L-Phenylalanine methyl ester hydrochloride

A solution of 88.5 parts of L-phenylalanine methyl ester hydrochloride in 100 parts of water is neutralized by the addition of dilute aqueous potassium bicarbonate, then is extracted with approximately 900 parts of ethyl acetate. The resulting organic solution is washed with water and dried over anhydrous magnesium sulfate. To that solution is then added 200 parts of N-benzyloxycarbonyl-L-aspartic acid-a-p-nitrophenyl, -benzyl diester, and that reaction mixture is kept at room temperature for about 24 hours, then at approximately 65°C for about 24 hours. The reaction mixture is cooled to room temperature, diluted with approximately 390 parts of cyclohexane, then cooled to approximately -18°C in order to complete crystallization. The resulting crystalline product is isolated by filtration and dried to afford -benzyl N-benzyloxycarbonvI-L-aspartyl-L-phenylalanine methyl ester, melting at about 118.5°-119.5°C. 

C HiiNOj 63-91-2) see Melphalan Quinapril hydrochloride Saquinavir L-phenylalanine fert-hutyl ester hydrochloride (CijHtoCINOj 15100-75-1) see Alacepril D-phenylalanine methyl ester (CioHijNOj 21685-51-8) see Nateglinide L-phenylalanine methyl ester hydrochloride (C10H14CINO2 7524-50-7) see Angiolensinatnide... 

In principle, aspartame is produced through the coupling of two amino acid moieties. One moiety consists of L-phenylalanine methyl ester hydrochloride (2) made by treating the amino acid in methanol and hydrochloric acid the other is aspartic acid anhydride hydrochloride or formic acid salt. The coupling reaction generates two positional isomers, a and p. 

L-Phenylalanine methyl ester hydrochloride L-Phenylalanine methyl ester, hydrochloride (9) (7524-50-7)... 

L-Phenylalanine methyl ester hydrochloride was purchased from Bachem California Inc. 

To a solution of L-phenylalanine methyl ester hydrochloride (25.0 g, 151 mmol) and Nibt O, (66.7 g, 483 mmol) dissolved in water (100 mL) was added benzyl chloride (57.5 g, 454 mmol), and the mixture was heated at 95 °C with stirring for 19 h. After the reaction mixture was cooled to ambient temperature, water (50 mL) and n-heptane (67 mL) were added and extracted. The organic layer was separated and washed twice with a mixed solution of methanol/water (1 2, 50 mL) and then dried over anhydrous Na2SO4. Concentration of the solution in vacuo provided Bu i-L-Phc-OMc (61.6 g, 85%) as a colorless oil. 

To a mixture of L-phenylalanine methyl ester hydrochloride (20.0 g, 93 nunol) suspended in toluene (93 mL) was added benzyl chloroformate (15.8 g, 93 nunol) with cooling in an ice bath. An aqueous solution of Na2CO3 (1 M, 130 mL) was added dropwise with vigorous stirring at 7 °C or lower. After this addition was complete, the mixture was stirred for 3 h. The organic layer was separated, washed with 0.1M HCl (60 mL) and saturated NaHCOs solution (60 mL), and then dried over anhydrous Na2SO4. Concentration of the solution in vacuo provided Cbz-L-Phe-OMe (28.8 g, 96%) as a colorless oil. 

Z-L-Asp(OH) -L-Phe-OMe is available from Indofine Chemical Co. (Somerville, NJ, USA). Z-L-Aspartic acid, Z-D-aspartic acid, L-phenylalanine methyl ester hydrochloride and D-phenylalanine methyl ester hydrochloride are from Sigma (St. Eouis, MO, USA). Acetic anhydride, methacrylic acid, 4-vinylpyridine, and ethylene glycol dimethacrylate are from Merck (Darmstadt, Germany). 2,2 -Azobis(2,4-dimethyl-valeronitrile) is fromWako Pure Chemicals Industries (Osaka, Japan). Anhydrous acetonitrile for polymer preparation is obtained from Eab-Scan (Dublin, Ireland). 

To a solution of L-phenylalanine methyl ester hydrochloride (10 mmol, 2.157 g) in water (10 mL) is added sodium carbonate decahydrate (10 mmol, 2.861 g). The solution is extracted with chloroform (2x20mL). The organic phase is separated and dried over anhydrous sodium sulfate. Removal of solvent under reduced pressure gives an oily product, which is stored at —20""C until further use. 

Diphenyl phosphoryl azide in dimethylformamide followed by triethylamine added at or below 0° to a soln. of N-carbobenzoxy-L-leucyl-L-leucine and L-valyl-L-phenylalanine methyl ester hydrochloride in the same solvent, stirred several hrs. at the above temp, and overnight at room temp. -> product. Y 87%. - Practically no racemization occurred. F. e., also direct prepn. of urethans from carboxylic acids (cf. Synth. Meth. 17, 393) by a simplified Curtius degradation, s. T. Shioiri, K. Ninomiya, and S. Yamada, Am. Soc. 94, 6203 (1972) Tetrah. Let. 1973, 2343 synthesis of N-subst. carboxylic acid amides and peptides with diethyl phosphoryl cyanide s. Tetrah. Let. 1973, 1595 coupling reagents in peptide synthesis, review, s. Y. S. Klausner and M. Bodansky, Synthesis 1972, 453 review of peptide synthesis s. J. Meienhofer, Chem. Technol. 3, 242 (1973). 

As shown in Scheme 3, diyne monomers 5a-f were designed to react with a series of commercially available amines and aldehydes. The polymerizatiOTi of diyne 5a, L-phenylalanine methyl ester hydrochloride 6, and formaldehyde 7 was first investigated and the effects of solvent, temperature, time, concentration. 

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