4-Methylmorpholine → tert.-butoxycarbonyl-D-phenylalanyl-glycine benzyl ester

Participants

Reaction Conditions

Reaction Steps

13.3 g (50 mmoles) of tert.-butoxycarbonyl-D-phenylalanine and 5.6 ml (50 mmoles) of N-methylmorpholine are dissolved in 50 ml of dimethyl formamide. The solution is cooled to -10° C., and 6.6 ml (50 mmoles) of isobutyl chloroformate are added with stirring. After 10 minutes the mixture is cooled to -20° C., and a solution of 18.6 g (55 mmoles) of glycine benzyl ester p-toluenesulfonate and 6.1 ml (55 mmoles) of N-methylmorpholine in 80 ml of dimethyl formamide, cooled to -20° C., is added. The reaction mixture is stirred at -10° C. for 10 minutes, at 0° C., for one hour, and then at room temperature overnight. The mixture is filtered and evaporated under reduced pressure. The residue is dissolved in a mixture of 300 ml of ethyl acetate and 100 ml of water. The ethyl acetate phase is separated and washed successively with 5% aqueous sodium hydrocarbonate solution (2×60 ml), water (2×60 ml), 1 n aqueous hydrochloric acid cooled with ice water (2×60 ml) and with water (2×60 ml) again, dried over sodium sulfate, decolourized with carbon, filtered, and the filtrate is evaporated under reduced pressure. The crystalline residue is suspended in a 1:1 mixture of diethyl ether and n-hexane, the solid is filtered off, washed with the above solvent mixture and dried in a vacuum desiccator. 18.95 g (91.9%) of tert.-butoxycarbonyl-D-phenylalanyl-glycine benzyl ester are obtained; m.p.: 133°-134° C., Rf14 =0.28-0.38, [α]D20 =+8° (c=1%, in dimethyl formamide).

Provenance & Evidence