Synthesis of an amino ester

Benzonitrile (1.520g, 14.8 mmol) was added to the THF solution of the sodium salt generated from (1) (1.830g, 14.8 mmol) by the action of sodium hydride (1.24 eq) at room temperature, and the resulting solution was stirred at 50°C for 16h. After addition of water (2ml) together with dichloromethane (70 ml), the mixture was dried over anhydrous sodium sulfate (without separation of the aqueous layer) and the solid phase was filtered off. Evaporation of the filtrate under reduced pressure and subsequent crystallization from dichloromethane/carbon tetrachloride/ cyclohexane (1 1 1) afforded (2) as a crystalline material (2.391 g, 10.5 mmol), m.p. 162-163°C (105 mg of (2) could be recovered by chromatography on silica gel of the mother liquor residue of evaporation the total yield of (2) was 75%). 

A mixture of (2) (2.439g, 10.7 mmol), acetic anhydride (1.5 ml, 15.9 mmol), and pyridine (1.0ml, 12.4mmol) in dichloromethane (10ml) was stirred for 4h at room temperature. After evaporation of dichloromethane, the residue was washed with water to give the thioester (3) (2.593 g, 9.64 mmol), m.p. 174-175.5°C. 

A solution of (3) (215mg, 0.799mmol) in methanol (10ml) was refluxed for 13h in the presence of two drops of triethylamine. After column chromatographic separation (silica gel, dichloromethane), crude methyl ester (4) (192mg, 0.759mmol) was obtained, m.p. 166-167°C (recrystallization from dichloromethane/carbon tctrachloride/n-hexane and water/methanol). Crude (4) thus obtained was treated with 

A -Acetylphenylglycine was obtained directly in a 91% yield when a solution of (3) in methanol/water (9 1) was refluxed for 3h in the presence of potassium carbonate (2 eq). A desulfurization by the methylthiolate anion produced by the hydrolysis of (3) accounts for this result [295]. In that way N-acetyl phcnylglycine was obtained in a 60% yield, by a three-step procedure, from benzonitrile. 

The method described above was applied to synthesize the methyl ester of Di.-/V-acetyl-5 hydroxytryptophan [294]. 

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