Water → (3S)-5-Oxo-4-(phenylmethyl)-3-morpholinecarboxylic acid

Participants

Reaction Conditions

Reaction Steps

A 5 L 3-neck round bottom flask was charged with (S)-(+)-N-benzylserine (229 g, 1.17 mol), sodium hydroxide (58.7 g, 1.47 mol), and water (1 L). The resulting solution was cooled to 0° C. and chloroacetyl chloride (170.4 g, 1.5 mol) added dropwise at a rate to maintain the temperature below 4° C. After addition was complete the reaction was stirred at 0° C. for 30 minutes. The cold bath was then removed and a solution of 30% sodium hydroxide (350 mL) added. An exotherm was observed and the reaction temperature reached 29° C. The reaction mixture was further heated to 33° C. and maintained at this temperature for 2 hours. Cooling to room temperature followed by acidification to pH 1 with 37% hydrochloric acid resulted in the formation of a thick white precipitate, which was isolated by filtration. The filter cake was slurried in acetonitrile (1 L), filtered, and the filtrate concentrated. Drying of the resulting solid afforded 68.1 g (25%) of (S)-(+)-4-benzylmorpholin-5-one-3-carboxylic acid as a crystalline white solid.

Provenance & Evidence