Dimethyl Sulfoxide → Benzyl 4-oxopiperidine-1-carboxylate

Participants

Reaction Steps

To a cooled solution (-78° C.) of oxalyl chloride (freshly distilled, 18.2 mL, 0.21 mol, 1.5 eq) in methylene chloride (1400 mL) under nitrogen was added freshly distilled dimethylsulfoxide (29.6 mL, 0.42 mol, 3.0 eq). The solution was stirred for 10 min after which a methylene chloride solution (150 mL) of 1-carbobenzyloxypiperidin-4-ol (described in example 87b) (32.76 g, 0.139 mmol) was added via cannula transfer. The solution was maintained at -78° C. for 30 min Triethylamine (116 mL, 0.83 mol, 6.0 eq) was added and the reaction warmed to room temperature over 1.5 h. Once at room temperature, the reaction was quenched with 3N HCl (400 mL). The organic phase was washed with 3N HCl (2×400 mL), 2.5N NaOH (2×400 mL) and saturated brine (1×400 mL). The methylene chloride phase was dried over anhydrous magnesium sulfate, filtered over 100 g of silica gel, and reduced to an oil. The procedure resulted in 23.8 g (73%) of the title compound which did not require any additional purification. 1H NMR (CDCl3, 300 MHz) 7.34 (m, 5H), 5.18 (s, 2H), 3.80 (t, J=6.2 Hz, 4H), 2.46 (br t, 4H) MS (CI, CH4) m/z 234 (M+1,39), 262 (M+29,10), 91 (100).

Provenance & Evidence