Water → (S)-2-hydroxy-1-(piperazin-1-yl)propan-1-one

Participants

Reaction Conditions

Reaction Steps

A flask charged with piperazine (10.0 g, 116 mmol) and (S)-ethyl 2-hydroxypropanoate 7 (17.84 g, 151 mmol, 1.30 equiv) was cooled to 10° C. Sodium methoxide (25 wt % in MeOH) (12.55 g, 58.1 mmol, 0.50 equiv) was slowly added while maintaining the temperature below 20° C. The cold water bath was removed and the reaction mixture was allowed to warm to ambient temperature and aged for 19 h. Water (6.23 g, 346 mmol, 3.0 equiv) was added and the mixture was aged for 16 h. The mixture was diluted with ethanol (40 mL) and concentrated under reduced pressure. The residue was diluted with ethanol (40 mL) and treated with a solution of oxalic acid dihydrate (6.58 g, 52.2 mmol) in ethanol (30 mL) to adjust the pH to 7.5. The suspension was cooled to <10° C., filtered through a pad of CELITE® and washed with ethanol (2×60 mL). The filtrate and washes were combined and concentrated to 50 mL. The solution was cooled to 10° C. and a solution of oxalic acid dihydrate (16.1 g, 128 mmol) in ethanol (60 mL) was slowly added. The suspension was allowed to warm to ambient temperature and stirred for 1 h. The suspension was cooled to 10° C. and the solid was collected by filtration, washed with cold ethanol (2×18 mL) and dried under reduced pressure at 50° C. for 24 h to afford the oxalate salt of (S)-2-hydroxy-1-(piperazin-1-yl)propan-1-one V as a white solid (15.2 g, 53%). 1H NMR (300 MHz, D2O) δ 4.73-4.51 (m, 1H), 3.93-3.59 (m, 4H), 3.26 (dd, J=8.8, 4.0 Hz, 4H), 1.27 (d, J=6.7 Hz, 3H).

Provenance & Evidence