Diethyl Ether → 4-Acetyl-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A 3-neck, 250 mL round bottom flask was charged with a solution of tert-butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (9.9 g) in Et2O (120 mL). The flask was purged with nitrogen and then cooled in a CO2/acetone bath. Methylmagnesium bromide (26.8 mL of a 3.0 M solution in Et2O, 80 mmol) was added dropwise over 10 min to the amide. The resulting thick mixture was warmed to 0° C. and then stirred for 40 min before being poured into 2 M HCl solution (50 mL). The mixture was diluted with Et2O (100 mL), washed with brine, dried (MgSO4) and concentrated on a rotary evaporator to give tert-butyl 4-acetylpiperidine-1-carboxylate (7.3 g, 32.1 mmol, 80% yield) as a colorless oil. The product partly crystallized on standing at RT. 1H-NMR (400 MHz, CDCl3) δ ppm 4.06 (2 H, s), 2.74 (2 H, s), 2.42 (1 H, s), 2.12 (2 H, s), 1.78 (2 H, s), 1.49 (2 H, s), 1.41 (9 H, s).

Provenance & Evidence