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

Participants

Reaction Steps

Ethanol (350 kg), Palladium (10% on activated carbon) (8.40 kg, 7.89 mol) and (S)-1-(4-benzylpiperazin-1-yl)-2-hydroxypropan-1-one 5 (70.0 kg, 282 mol) were charged to a reactor and the mixture was purged with nitrogen and heated to reflux. Cyclohexene (70.0 kg, 852 mol) was slowly added. The reaction mixture was heated to reflux and stirred for 24 h. After cooling to ambient temperature, the mixture was filtered through a pad of CELITE® and the cake was washed with ethanol (20 kg). The filtrate was cooled to 10-15° C. and a solution of oxalic acid dihydrate (36.0 kg, 286 mol) in tetrahydrofuran (156 kg) was slowly added at a rate to maintain the reaction temperature at 10-20° C. After aging for 2 h, the solid was collected by filtration, washed with ethanol (100 kg) and dried under reduced pressure at 50-55° C. to afford (S)-2-hydroxy-1-(piperazin-1-yl)propan-1-one oxalate salt V (58.2 kg, 83%). 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