Methyl L-phenylalaninate hydrochloride

Set-Up and Reaction Place 0.63 g of methyl L-phenylalaninate hydrochloride in a 50-mL Erlenmeyer flask. Add 10 ml of dimethylformamide and 0.3 ml of A/-methylmorpholine to the flask, swirl the flask to mix the contents, and place the flask in an ice-water bath. Label the flask as Solution A. 

Consider the spectral data for methyl L-phenylalaninate hydrochloride (Figs. 24.9 and 24.10). 

Discuss the differences observed in the IR and NMR spectra of L-phenylala-nine and methyl L-phenylalaninate hydrochloride that are consistent with the formation of the latter in this procedure. 

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. 

D-Phenylalanine methyl ester is prepared from D-phenylalanine methyl ester hydrochloride in the same way as that for L-Phenylalanine methyl ester. 

To a solution of L-phenylalanine methyl ester (8 mmol, 1.434 g) in dimethyl sulfoxide (60 mL) is added Z-L-aspartic anhydride (8 mmol, 1.994 g) under stirring. The reaction continues at 20°C for S h. The reaction mixture is then poured into distilled water (1.2 L). Acidification with 1M hydrochloride acid (7-8 drops) gives a crude product as white precipitate. This is separated by filtration, dried in a vacuum and re-crystallized from ethyl acetate. Optical activity ([a]o) in methanol +10.0. 

A/-Methacryloyl-D,L-phenylalanine Methyl Ester. The enantiodiscrim-inating influence of cyclodextrin in the free-radical polymerization of the racemic monomer iV-methacryloyl-D,L-phenylalanine methyl ester (2e) (41) was investigated for the first time. 2e was synthesized in 99% yield by the reaction of phenylalanine methyl ester hydrochlorides with methacryloyl chloride in the presence of triethylamine. The racemic monomer was subsequently added to an aqueous solution of RAMEB yielding a clear colorless solution of complexed monomer. Homopolymerizations were carried out in the presence of redox initiator at various temperatures. It was showed that the L-enantiomer is enriched in the residual monomer mixture. This observation confirms that complexed D-enantiomer polymerizes faster than the complexed L-enantiomer. No polymerization of 2e was observed without cyclodextrin under the same conditions. 

Figure 25 Fluorescence response upon addition of various analytes into a solution of 49 (0.1 mM) and 52 (1.0 mM). Acetylcholine (o), glycine ( ), L-aspartic acid (A), L-proline ( ), L-phenylalanine ethyl ester hydrochloride ( ), and glycine methyl ester hydrochloride (<>). (Adapted from Ref. 58. American Chemical Society, 1996.)...

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). 

Carbobenzoxy-L-phenylalanine dissolved in ethyl acetate with addition of pyridine, treated with di(p-nitrophenyl) carbonate, refluxed 3hrs., L-proline methyl ester hydrochloride in chloroform and triethylamine added, allowed to stand overnight at room temp., then the volatiles removed by distillation in vacuo crude carbobenzoxy-L-phenylalanyl-L-proline methyl ester. Y 87%. F. e. s. T. Wieland et al., A. 655, 189 (1962) cf. P. G. Katsoyannis et al., Am. Soc. 85, 1679, 1681 (1963) also reactions with 2,4-dinitrophenyl esters s. R. Glatthard and M. Matter, Helv. 46, 795 (1963). 

L-Phenylalanine, 5 moles of dimethyl sulfite, and 1.1 moles of anhydrous p-toluenesulfonic acid heated 4.5 hrs. on a steam bath L-phenylalanine methyl ester p-toluenesulfonate. Y 99%.—This method is of advantage if the p-toluenesulfonates are more readily purified than the hydrochlorides (best prepn. of the latter with SOGlg, s. Synth. Meth. 9, 344). F. e., also benzyl esters, s. J. M. Theobald, M. W. Williams, and G. T. Young, Soc. 1963, 1927. 

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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