Method for ion-exchange separation of mixture of phenylalanine and tyrosine

FIELD: amino acids, chemical technology.

SUBSTANCE: invention relates to methods for separation and isolation of individual aromatic amino acids from their mixtures. Proposed method is carried out by multiple-stage procedure by continuous passing the parent solution of mixture of phenylalanine and tyrosine through column packed with strong-base anion-exchange resin AV-17-2P in OH-form and in periodic change of temperature regimen. After saturation of sorbent with amino acids the process is carried out by turns at two temperature values by collecting two fractions in outlet. At value T1 = 20°C eluate is enriched with tyrosine as one component of the solution and at value T2 = 80°C - with another component, i. e. phenylalanine. By changing volumes of fractions colleted at different values of temperature the method provides, if necessary, to enhancing degree of purification of one component of the mixture. Process can be carried out both in mono- and multi-stage regimen and both different columns and a single the same column can be used as different stages. Proposed invention provides the separation method that results to the enhanced effectiveness for separation of mixture of phenylalanine and tyrosine and excluding accessory reagent from the technological process used in regeneration and conversion of ion-exchange resins to working form, elimination of flows and enhanced yield of amino acids. Invention can be used in chemical, microbiological, food processing industry and agriculture.

EFFECT: improved separating method.

4 cl, 6 tbl, 4 ex

 

The invention relates to methods of division and separation of individual aromatic amino acids from mixtures thereof and can be used in chemical, microbiological, food industry, agriculture.

Known methods for isolating amino acids, which are based on classical ion-exchange chromatography [A.S. USSR №438256, C 07 C 99/12, 1977, A.S. USSR №644782, C 07 C 99/12, 1979, as the USSR №639862, C 07 C 99/12, 1978, A.S. USSR №979991, G 01 N 31/08, 1981, A.S. USSR №960163 C 07 C 99/12, 1982]. The disadvantages of these methods are used for sorbent regeneration of a significant number of auxiliary reagents, availability of preliminary preparation of amino acid solutions before passing through the ion exchanger. The closest to this invention is the method of separation of tryptophan and phenylalanine (RF patent No. 2186056, C 07 C 227/40, 2002), lack of which is the incomplete separation of amino acids.

The objective of the proposed method is increasing the efficiency of separation of the mixture of phenylalanine and tyrosine by excluding from the process of auxiliary chemicals used for regeneration and translation in a working form ion exchangers, refuse sewage and enhance the yield of amino acids.

This object is achieved in that in the known method of ion-exchange separation of phenylalanine and tyrosine, on the expectation by passing the mixture through the column, filled with anionite AV-17-2P in the form, and fractional excretion solutions of phenylalanine and tyrosine, according to the invention the process is carried out multi-stage and second and subsequent stages can be used in two columns, where the solution of phenylalanine and tyrosine continuously passed through the column (s) in the periodic temperature change not less than 20°in the range of 20-80°With, at first, the sorbent is saturated with amino acids, passing the mixture of solutions of amino acids at the first temperature value, then through the sorbent miss the same mixture of amino acids at the second temperature value, collect the eluate enriched in one of the amino acids, followed by regeneration of the same mixture at the first temperature value, collecting the eluate enriched by another amino acid, which was depleted in the previous fraction, and then continuously cyclically repeat the process.

As a result, get two fractions having different ratio of the concentrations of amino acids, and, by varying the ratio of the volumes collected at different temperatures fractions, reach, if necessary, increasing the purity of one of the components. The process can be arranged as single-and multistage, and as different levels can be used as various speakers and odni same column. To ensure the orientation process each subsequent stage may consist of a pair of columns is smaller in comparison with the previous stage, the cross-section. On the second and subsequent steps of the process in the various fractions obtained in the previous step, and one of the obtained fractions are sent for further processing, and the second, if necessary, re-process on the previous stage. The degree of separation greater than obtained with known methods, and for the expense of processing sorbent auxiliary reagents is achieved in the absence of sewage and, accordingly, eliminates the ablation products in the drains.

The lower temperature level due to the fact that maintaining the temperature below 20°requires the use of cooling equipment. The upper bound (80° (C) temperature limited temperature stability of the partial amino acid.

Example 1. Separation of phenylalanine (Hairdryer) and tyrosine (Tyr) is carried out in temperature-controlled ion exchange column (0.5 cm2filled with anionite AV-17-2P in HE form in the amount of 6 g in terms of dry resin. The layer height of 30 cm, the volume of a layer 15 ml. of T1=20°C, T2=80°C. the Original solution has a concentration of the dryer 1 g/l and Tyr 0.4 g/l and was obtained by dissolving the partial amino acid in 0.1 M NaOH solution. The transmission rate R is the target of 2 ml/min Control over the content of the partial amino acid in solution hereinafter were carried out spectrophotometrically according to the method proposed in [GAH, 2000, T, No. 4. - S-377].

First by the saturation of the layer of sorbent amino acids, which passed through the column of 1.75 l of the starting solution at T1. Collect the output solution contains a Hairdryer at a concentration of 0.08 g/l and a shooting range in trace quantities. It can be directed by evaporation to obtain a dry Hairdryer with a purity of up to 89%. Passing the solution continue at T2and T1alternately. Thus collected fraction 2 HP component Concentration at the outlet of the column shown in table 1. The process continuously.

Table 1
Concentration (g/l) component output from the column in example 1
No. of cycleT2T1
Hair dryersTyrHair dryersTyr
10,940,451,150,24
2 and later0,860,551,140,25

Starting from the second cycle, the composition of the collected fractions becomes constant is passed. During one cycle of 4 l of the starting solution get 2 liters of solution enriched containing Tyr and Tyr at a concentration of 0.55 g/l and a Hairdryer in the concentration 0,86 g/l, and 2 l of a solution enriched with a Hairdryer and contain a Hairdryer in the concentration of 1.14 g/l, and Tyr at a concentration of 0.25 g/l in the single-stage process is achieved by reduction of impurities tyrosine in solution Hairdryer 1.6 times and increase the percentage of Tyr in enriched them faction 1.4 times. This group contains a Tyr in the form of a supersaturated solution from which the Tyr residue without prior evaporation in the form of crystals of almost pure drug, not contaminated (at the stage of evaporation) of the decomposition components.

Example 2. If necessary, may conduct a multi-stage process. As a first-degree use the column with cross-section 1 cm2the number of ion exchanger 6 g, the layer height 20 cm, layer volume 20 ml of the Original solution has a concentration Hairdryer 1.2 g/l and Tyr 0.4 g/l and was obtained by dissolving the partial amino acid in 0.1 M NaOH solution. Bandwidth solution of 4 ml/min

For saturation at 293 K (T1pass 3,1 l of solution. The eluate contains the Hairdryer at a concentration of 0.01 g/l and a shooting range in trace quantities. Then, the solution is passed alternately at T2and T1. Collect fractions of 0.5 L. the Concentration of the components on o the de from the column are presented in table 2.

Table 2
Concentration (g/l) component output from the column first step in example 2:
T2T1
No. of cycleHair dryersTyrHair dryersTyr
11,120,211,280,11
2 and later1,120,291,280,11

As a second stage of use of the column, similar to that described in example 1. Through the first of them is passed to the first stage at T2solution. For saturation miss a 1.75 l of a solution at T1. By further passing the solution collected fractions 2.25 l at each temperature. The concentration of the components in the eluate are presented in table 3. The process continuously. Starting from the 2nd cycle, the composition of collected fractions constant.

Through the second column of the second stage flow solution obtained in the first stage at T1. For saturation pass 1.8 l of solution at T1. By further passing the solution collected fractions 2.25 l at each temperature. The concentration of the components in the eluate reached the Lena in table 4. The process continuously. Starting from the 2nd cycle, the composition of collected fractions constant.

Table 3
Concentration (g/l) components at the outlet of column 1 of the second step in example 2:
No. of cycleT2T1
Hair dryersTyrHair dryersTyr
11,060,361,230,16
2 and later1,010,411,280,16
Table 4
Concentration (g/l) components at the output of the 2 columns of the second step in example 2:
No. of cycleT2T1
Hair dryersTyrHair dryersTyr
11,260,131,530,06
2 and later1,230,161,330,03

Thus, in the two hundred the applications process get 4 equal volume fractions, one of them contains a Hairdryer at a concentration of 1.33 g/l and shooting at a concentration of 0.03 g/l, the second - 1,01 and 0.41 g/l, respectively. Two fractions have the component concentration close to the source, and can be re-directed for processing. In the two-stage process is achieved by reduction of impurities Tyr in solution Hairdryer 3.4 times increase in the percentage of Tyr in enriched fractions in them 2 times.

Example 3. The column described in example 1, saturated with amino acids in the same way. To improve the degree of purification of the dryer from the shooting range at the outlet from the column at T2collect the fraction by volume of 5 l, and T1- 0,5 HP component Concentration at the outlet of the column are presented in table 5. The process can continue uninterrupted.

0,42
Table 5
Concentration (g/l) component output from the column in example 3:
No. of cycleT2T1
Hair dryersTyrHair dryersTyr
10,970,431,180,20
20,980,411,180,20
3 or later0,981,180,20

Starting with 2-3 cycles, the composition of the collected fractions is permanent. During one cycle of 5,5 l initial solution get 0.5 l of the solution containing the dryer at a concentration of 1.18 g/l and shooting at a concentration of 0.20 g/l, and 5 l of a solution containing components in concentrations of 0.98 and 0.42 g/l, respectively. In single-stage process reach 2-fold purification hair dryers.

Example 4. In the first stage separation Hairdryer and Tyr produced in accordance with example 2. After 7 cycle passing the solution ceased. In the second stage as the second stage uses the same column, through which without pre-saturation miss previously obtained at T2solution. The output is collected fractions 4.5 l at each temperature. At the end of the available bandwidth of the solution through the same column without prior saturation pass obtained in the first phase at T1solution. The output is collected fractions 4.5 l at each temperature. The concentration of components at the output presented in table 6.

Table 6
Concentration (g/l) component output from the column in example 4:
No. of cycleT2 T1
Hair dryersTyrHair dryersTyr
The first stage
The transmission source solution
11,120,211,280,11
2-71,120,291,280,11
The second stage
Passing the solution obtained in the first phase at T2
11,070,341,240,16
2-31,010,411,230,17
The third stage
Passing the solution obtained in the first phase at T1
11,080,330,310,08
2-31,230,161,310,08

Thus, the use at different stages of the same column allows to achieve the same degree of separation as in example 2. Meanwhile at the expense of continuity is the process is achieved by reducing the number of equipment used.

1. The method of ion-exchange separation of phenylalanine and tyrosine, which includes passing the mixture through a column filled with anion exchange resin AV-17-2P in the form, and fractional excretion solutions of phenylalanine and tyrosine, wherein the process is carried out multi-stage and second and subsequent stages can be used in 2 columns, where the solution of phenylalanine and tyrosine continuously passed through the column(s) in the periodic temperature change not less than 20°in the range of 20-80°With, at first, the sorbent is saturated with amino acids, passing the mixture of solutions of amino acids at the first the temperature value, then through the sorbent miss the same mixture of amino acids at the second temperature value, collecting the eluate enriched in one of the amino acids, followed by regeneration of the same mixture at the first temperature value, collecting the eluate enriched by another amino acid, and then continuously cyclically repeat the process.

2. The method according to claim 1, characterized in that one of the fractions in each column of the second and subsequent stages, is sent for further processing, and the second can be re-processed in the previous step.

3. The method according to claim 1, wherein varying the ratio of the volumes collected at different values of temperature fractions.

4. The way p is 2, wherein the multi-stage separation is carried out on the same column, operating in the continuous mode.



 

Same patents:

The invention relates to pharmaceutical industry and medicine and relates to products containing derivatives of gamma-aminobutyric acid and affecting the cardiovascular system

The invention relates to a new method for obtaining compounds of formula 6, which includes obtaining the solution of the compounds of formula 2 by successive addition of the compounds of formula 1 in an aprotic solvent And, taken in an amount 4-30 mg/g, aprotic solvent, taken in an amount of 0.0001-0.25 ml/g, with stirring in an atmosphere of inert gas, and adding an activating agent, taken in an amount of 0.95 to 2.0 mol/mol from the specified connection 1; obtaining the compounds of formula 4 by successive addition of the compounds of formula 3 and the base, taken in an amount of 1.9 to 3.0 mol/mol to a mixture of aprotic solvent B, taken in an amount of 3-30 mg/g and proton solvent, taken in an amount of 3 to 30 ml/g from the specified connection 3, at a temperature of from -20oWith up to the temperature of reflux distilled the above-mentioned mixture and maintaining the pH of this mixture 8-13; obtaining the compounds of formula 5, which includes, in series, add the specified solution to the above-mentioned mixture in the atmosphere of inert gas while maintaining the specified temperature, followed by curing the resulting mixture to reach room temperature and adding thereto an organic solvent in an amount of 3-30 ml/g, ekstragirovanie the water layer and organic layer And, processing the specified organic layer And an aqueous solution of the acid or aqueous acid solution and water, separating the aqueous layer B from the organic layer B, where M+represents a monovalent cation, provided that, if M+is N(C1-C6alkyl)4+after the specified grounds for the specified mixture of Tetra - C1-C6alkylamine halide

The invention relates to the production of new labeled analogue of physiologically active compounds O-(4-hydroxy-3,5-diiodophenyl)-3',5'-diiodo-L-tyrosine ("t") the compounds of formula 1, which can be used in organic chemistry, biology and medicine
The invention relates to methods for selection of individual amino acids from mixtures thereof and can be used in chemical, food, microbiological industry and agriculture

The invention relates to a method for obtaining compounds of formula I, where X denotes the radical, inert under the conditions of the reaction; m is 0; R3denote hydrogen, CH3CH2F or CHF2Y denotes a group OR4N(R5)2or N(CH3)OCH3; R4and R5each independently of one another denotes hydrogen or C1-C8alkyl or (R5)2together with the nitrogen atom to which they are bound, form a 5 - or 6-membered unsubstituted or substituted ring, according to which (a) conduct the interaction of the compounds of formula II, where X and m have the above for formula I, values and R1and R2each independently of one another denote WITH1-C6alkyl, C1-C6alkenyl, C1-C6alkoxyalkyl or3-C6cycloalkyl or R1and R2together with the nitrogen atom form an unsubstituted or substituted 6 - or 7-membered ring which in addition to the nitrogen atom may contain an additional nitrogen atom, in an aprotic solvent with an organolithium compound of formula III, where R7denotes an organic anionic radical; b) carry out the interaction of the obtained lithium complex with the compound of the formula IV, where)2or N(CH3)OCH3; R4stands WITH1-C8alkyl; R6represents C1-C8alkyl; or R6)2together with the nitrogen atom to which they are bound, form a 5 - or 6-membered unsubstituted or substituted ring with obtaining the compounds of formula V; C) is connected in any order in 1) is subjected to occimiano 0-methylhydroxylamine or are occimiano hydroxylamine, and then methylated, formatierung or diftormetilirovaniya; 2) enter into interaction with the ether of Harborview acid

The invention relates to methods for obtaining optically active ester of Erythro - 3-amino-2-hydroxybutyric acid, which represents an important intermediary product pharmaceutical reagents, in particular inhibitor of HIV protease
The invention relates to a method for obtaining hydrochloride-amino--phenylalkanoic acid (drug phenibut) by reduction with hydrogen derived phenylcarbinol acids, and the derivatives phenylcarbinol acids used replaced by-phenylpropionate acid or their esters of the General formula C6H5-CH(R')-CH(R")-COO(R') where R' = CH2NO2CN; R" IS H, COOH; R' = H, CH3C2H5and the hydrogenation is carried out in the presence of palladium catalysts at a temperature of 20-75°C With subsequent processing of the obtained product with hydrochloric acid

-phenylazomethine and its analogues, derivatives-phenylazomethine, derivatives of azetidinone" target="_blank">

The invention relates to a method for producing beta-phenylazomethine and its analogues of General formula (I) of the aromatic aldehyde and alpha methylaniline-S with an intermediate passage of the lactam of General formula (II)

The invention relates to methods of stereoselective get driving phenylazomethine General formula

< / BR>
in which R denotes a phenyl radical or a radical of tributoxy;

R1denotes a protective group of the hydroxy function group
The invention relates to methods for selection of individual amino acids from mixtures thereof and can be used in chemical, food, microbiological industry and agriculture

FIELD: amino acids, chemical technology.

SUBSTANCE: invention relates to methods for separation and isolation of individual aromatic amino acids from their mixtures. Proposed method is carried out by multiple-stage procedure by continuous passing the parent solution of mixture of phenylalanine and tyrosine through column packed with strong-base anion-exchange resin AV-17-2P in OH-form and in periodic change of temperature regimen. After saturation of sorbent with amino acids the process is carried out by turns at two temperature values by collecting two fractions in outlet. At value T1 = 20°C eluate is enriched with tyrosine as one component of the solution and at value T2 = 80°C - with another component, i. e. phenylalanine. By changing volumes of fractions colleted at different values of temperature the method provides, if necessary, to enhancing degree of purification of one component of the mixture. Process can be carried out both in mono- and multi-stage regimen and both different columns and a single the same column can be used as different stages. Proposed invention provides the separation method that results to the enhanced effectiveness for separation of mixture of phenylalanine and tyrosine and excluding accessory reagent from the technological process used in regeneration and conversion of ion-exchange resins to working form, elimination of flows and enhanced yield of amino acids. Invention can be used in chemical, microbiological, food processing industry and agriculture.

EFFECT: improved separating method.

4 cl, 6 tbl, 4 ex

FIELD: separation and cleaning of para-aminobenzoic acid.

SUBSTANCE: proposed method consists in increasing the concentration of salts of para-nitrobenzoic acid in reaction mass by obtaining the following ratio of sodium and ammonium salts: Na-salt : NH4-salt = 7.5-8.0 : 2.5-2.0 mole; acidation of solution of para-aminobenzoic acid is carried out with the aid of nitric acid at concentration of 20-25%. Novelty of invention consists in setting the required ratio of sodium and ammonium salts of para-nitrobenzoic acid and use of nitric acid for separation of para-aminobenzoic acid from solution.

EFFECT: increased productivity of equipment; high concentration of salts of para-nitrobenzoic acid; high purity of target product.

2 cl, 1 tbl, 4 ex

FIELD: preparative chemistry and technology.

SUBSTANCE: invention relates to a method for separating in fractionating a solution containing betaine and sucrose. Method involves chromatographic fractionation of this solution, nanofiltration and regeneration of fraction enriched with betaine and, possibly, fraction enriched with sucrose. Chromatographic separation is carried out in columns filled with material chosen from cation-exchange and anion-exchange resins, and nanofiltration is carried out with a membrane for nanofiltration chosen from polymeric and inorganic membranes having the limit value of passing through a column from 100 to 2500 g/mole. Solution for fractionation represents a solution prepared from sugar beet, for example, the black syrup solution.

EFFECT: improved method of betaine regeneration.

40 cl, 12 tbl, 3 dwg, 7 ex

FIELD: food industry, medicine.

SUBSTANCE: invention relates to a method for production of highly purified amino acid mixtures. Method involves separation of suspended particles and clearing protein hydrolyzate on clearing sorbent. Ammonia is removed from hydrolyzate by its passing through desalting system at the rate from 2 to 3 volumes per volume of desalting system/h followed by carrying out sorption of amino acids on cation-exchange resin in H+-form. Amino acids are eluted from cation-exchange resin with alkali solution and eluate is subjected for microfiltration and drying. Desalting system represents a system of succession connected ion-exchange column with alternating cation-exchange resin - anion-exchange resin wherein volume of anion-exchange resin provides exceed of its full ion-exchange capacity by 20-25% as compared with that in cation-exchange resin. Method provides enhancing effectiveness of ion-exchange purification of amino acids.

EFFECT: improved preparing method.

6 cl, 2 dwg, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention concerns separation of free gene-coded amino acid mix by method of capillary electrophoresis and can be applied in quality control for medicines and in defining amino acid composition of bioactive peptides. Sodium dihydrophosphate solution with methanol (pH 1.9-2.1) added is proposed as background electrolyte. Analysis is performed at +9-+11 kV voltage. The result is enhanced selectivity of free gene-coded amino acid separation leading to complete separation of 16 amino acid mix.

EFFECT: possibility of amino acid analysis of bioactive peptides.

1 cl, 1 ex, 2 tbl

FIELD: chemistry; biochemistry.

SUBSTANCE: invention pertains to biotechnology. Disclosed is a method of extracting L-lysine from culture fluid. Biomass-free culture fluid is acidified to pH 1.9-2.3. Lysine is sorbed from the obtained solution on a sulphocationite strongly cross-linked with polystyrene to saturation or close to saturation state. The cationite is washed from said solution with water at temperature 70-85°C and consumption of desalinated water is equal to 1.1-1.3 times the volume of the ionite layer. Elution is carried out with 5% ammonia solution. The lysine-containing fraction is collected when pH 6-7 is attained. A sulphur-containing antioxidant is added to the lysine-containing fraction in amount of 0.28-0.43%. Primary vacuum-evaporation of the fraction is carried out with concentration of the solution 2.3-2.8 times. The obtained concentrate is neutralised with hydrochloric acid. Said concentrate is adsorptionally clarified on a macroporous weakly basic anionite of the condensation type. Secondary vacuum evaporation is carried out. Lysine monochlorohydrate is then crystallised. The crystals are separated from the mother solution and dried at temperature 85-90°C.

EFFECT: process of extracting L-lysine is characterised by high purity of the crystalline product of 99,1-100% with level of irreversible loss lower than 6,1%.

2 cl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method for ion-exchange separation of methionine and glycine and can be used in biochemistry, pharmaceutical and food industry. The method involves separation of methionine and glycine in two steps. At the first step amino acids undergo sorption with enrichment of the sorbent phase with glycine, and the solution at the output enriched with methionine. For this purpose, polyampholyte Purolite S950 in H-form is prepared. The mixture of two aliphatic amino acids undergoes sorption in a countercurrent column with a fixed sorbent layer. For this purpose, a solution containing a mixture of glycine and methionine is fed from below and glycine is undergoes sorption on polyampholyte Purolite S950. Methionine, appears at the output, the aqueous solution of which is sorbed in a receiver at the output of the column and after a certain time - the amino acids. Sorption is stopped. During sorption, samples are collected at defined time intervals. Total concentration of amino acids is controlled using an iodimetric method, and concentration of methionine is controlled using a spectrophotometric method, while glycine concentration is controlled based on concentration difference: between total concentration and methionine concentration. The degree of separation of the initial solution is equal to 60%. At the second step, glycine is eluted with hydrochloric acid solution at pH 1.2 from the sorbent while feeding glycine-containing eluate from the top, and sorbed in the receiver. Concentration of glycine is equal to 70%. After desorption of glycine, the mixture of amino acids undergoes complete desorption. Polyampholyte takes the initial shape and is ready for operation. Samples are collected at defined time intervals and each sample is analysed using iodometric and spectrophotometric methods. For complete separation of glycine from methionine, the two-step process of separating the mixture of amino acids obtained at the output of the column is repeated.

EFFECT: method enables efficient separation of methionine and glycine by combining sorption and desorption processes while excluding the sorbent regeneration step, and reduce the volume of wash water without using considerable amount of auxiliary reactants.

2 dwg, 2 tbl, 1 ex

FIELD: biotechnology.

SUBSTANCE: biomass is isolated by microfiltration. The native solution is clarified. The clarified solution is desalted by passing through the ion-exchange system of 10 identical columns with a height to diameter ratio of 0.8, which are connected in the sequence: anion exchanger in OH-form - cation exchanger in H+-form, at a rate of 2-2.5 of solution volume per volume of the system. The desalted solution is passed through the column with the anion exchanger in OH-form. The resulting solution of lysine-base is passed through the column with the cation exchanger. Elution of lysine with cation exchanger 3-5N is carried out, preferably 4N, with alkali liquor. The gaseous hydrogen chloride is bubbled to the resulting concentrated lysine eluate, causing simultaneously neutralisation and crystallisation of lysine.

EFFECT: method enables to eliminate the need of evaporation in the technological, which results in power consumption economy.

2 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method for producing a compound of formula IIIa, where R is an alkyl group with 1-5 carbon atoms; X is a protecting group for an alcohol selected from benzyl (Bn), methoxymethyl (MOM), 2-methoxyethoxymethyl (MEM), methylthiomethyl (MTM), tetrahydropyranyl (THP), benzyloxymethyl (BOM), p-methoxyphenyl, p-methoxybenzyl (MPM ), p-methoxybenzyloxymethyl (PMBM), triisopropylsilyl (TIPS), tert-butyldimethylsilyl (TBDMS), 2-(trimethylsilyl) ethoxymethyl (SEM), and (phenyldimethylsilyl)methoxymethyl (SMOM); Y is a protecting group for an amine selected from tert-butylcarbamate (Boc), 9-fluorenylmethylcarbamate (Fmoc), methyl carbamate, ethyl carbamate, 2-chloro-3-indenylmethylcarbamate (Climoc), benz[f]inden-3-ylmethylcarbamate (Bimoc) 2,2,2-trihloretilkarbamata (Troc), 2-chlorethylcarbamate, 1,1-dimethyl-2,2-dibromethylcarbamate (DB-t-BOC), 1,1-dimethyl-2,2,2-trichlorethylcarbamate (TCBOS) benzylcarbamate (Cbz) and diphenylmethylcarbamate. Disclosed method comprises a processing method comprising steps of 1)-5). At step 1) providing a crude reaction product comprising said compound of formula IlIa; 2) adding ethyl acetate to crude reaction product of step (1) to obtain a suspension;3) adding water to suspension of step (2) to form a biphasic system comprising an aqueous phase and an organic phase, and discarding aqueous phase;4) adding an acid to organic phase of step (3) to form a biphasic system comprising an acidic aqueous phase and an organic phase, and discarding acidic aqueous phase;5) washing organic phase of step (4) with water. Invention also relates to methods of producing compounds of formulae Va and VI and can be used in synthesis of radiopharmaceutical precursors for positron emission tomography.

EFFECT: proposed method enables to avoid formation of emulsions during synthesis on an industrial scale and obtain a diphasic system with good separation.

14 cl, 1 ex

Up!