Dimethyl Sulfoxide → (2S)-1-tert-butoxycarbonyl-2-phenylpiperidin-3-one

Temperature

-70 °C

Dimethyl sulfoxide (20.80 ml, 22.90 g, 29.3 mmol) in dichloromethane (75 ml) was added dropwise to a cooled (−70° C.) solution of oxalyl chloride (13.95 ml, 20.30 g, 160 mmol) in dichloromethane (350 ml). The mixture was stirred at −70° C. for 15 minutes, then (2S,3S)-1-tert-butoxycarbonyl-3-hydroxy-2-phenylpiperidine (prepared by the method described in European Patent Specification number 0 528 495-A; 36.91 g, 133 mmol) in dichloromethane (150 ml) was added dropwise. The mixture was stirred at −70° C. for 20 minutes, then allowed to warm to −30° C. The mixture was cooled to −50° C. and triethylamine (55.95 ml, 40.45 g, 400 mmol) was added slowly. The mixture was allowed to warm to 0° C. and diluted with ice-cooled dichloromethane (250 ml). The mixture was washed with ice cold aqueous citric acid solution (5%, 2×300 ml) and water (300 ml), dried (MgSO4), and the solvent was evaporated under reduced pressure to give the title compound as a yellow oil (42.3 g), which was used immediately without further purification. 1H NMR (250 MHz, CDCl3) δ 7.5-7.3 (5H, m), 5.8 (1H, br s), 4.2 (1H, br s), 3.4 (1H, m), 2.6 (2H, m), 2.0 (2H, m), and 1.54 (9H, s).

1. stirringThe mixture was stirred at −70° C. for 20 minutes
2. temperatureto warm to −30° C
3. temperatureThe mixture was cooled to −50° C.
4. temperatureto warm to 0° C.
5. additiondiluted with ice-
6. washThe mixture was washed with ice cold aqueous citric acid solution (5%, 2×300 ml) and water (300 ml)
7. dry with materialdried (MgSO4)
8. customthe solvent was evaporated under reduced pressure

ORD record

ord-fae6689def764c2187c434bf4f0df34d

Source dataset

uspto-grants-2001_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06172077B2