Chloroacetyl chloride → (5R)-5-Phenylmorpholin-3-one

Participants

Reaction Steps

To a mixture of (2R)-2-amino-2-phenyl-ethanol (10 g, 72.90 mmol) and triethylamine (18.45 g, 25.41 mL, 182.3 mmol) in THF (207.5 mL) at 0° C., was added 2-chloroacetyl chloride (8.234 g, 5.799 mL, 72.90 mmol) over 5 mins. The reaction mixture was partitioned between EtOAc (100 mL) and water (100 mL) and the organic layer separated, washed successively with water (2×100 mL), brine (1×100 mL), dried over MgSO4, filtered and concentrated in vacuo. The crude product was then dissolved in THF (145.2 mL) and NaH (60% in mineral oil) (3.499 g, 87.48 mmol) was added portionwise over 5 mins at rt. On complete addition, the resulting mixture was stirred at rt for 1.5 h. The reaction mixture was quenched with saturated aqueous ammonium chloride solution (50 mL) and diluted with EtOAc (50 mL) and the organic layer separated, washed with sequentially with water (2×50 mL) and brine (1×50 mL), dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by ISCO column companion system (330 g column, 0-10% MeOH/CH2Cl2). Product fractions were combined and concentrated in vacuo to leave the product as a pale yellow solid (5.2 g, 41% yield); 1H NMR (400.0 MHz, DMSO) d 3.55 (1H, m), 3.96 (1H, m), 4.08 (2H, s), 4.63 (1H, m), 7.29-7.40 (5H, m) and 8.46 (1H, s) ppm.

Provenance & Evidence