Dimethyl Sulfoxide → 4-(4-Methoxyphenyl)-1-(1-(4-methylbenzyl)-2-oxopyrrolidin-3-yl)piperidin-3-one

Participants

Reaction Conditions

Reaction Steps

A mixture of DMSO (0.17 mL, 2.46 mmol) and DCM (4 mL) was cooled to −78° C., and oxalyl chloride (0.2 mL, 2.3 mmol) was added dropwise over 2 min. Following the addition, the mixture was stirred at the same temperature for 10 min. To the reaction was then added dropwise (±)-rel-3-((3R,4R)-3-hydroxy-4-(4-methoxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one (375 mg, 0.95 mmol, mixture of four diastereomers from step E) in DCM over 5 min. The mixture was stirred for 1 h, and then triethylamine (1 mL, 7.6 mmol) was added and the mixture was stirred for 15 min, slowly warmed to rt, and then extracted with 3×40 mL of DCM. The combined organic layers were washed with 50 mL of brine, dried over Na2SO4, filtered, and concentrated under vacuum to yield 345 mg of 4-(4-methoxyphenyl)-1-(1-(4-methylbenzyl)-2-oxopyrrolidin-3-yl)piperidin-3-one (as a mixture of 4 diastereomers), which was used directly in the next step. LCMS (method)) RT 1.12 min, m/z 393 (M+H+), 411 (M+H++18), 1.18 min, m/z 393 (M+H+).

Provenance & Evidence