Triethylamine → tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

Participants

Reaction Steps

A solution of 1-(1,1-Dimethylethyloxycarbonyl)-4-piperidine carboxylic acid (11.3 g, 49.3 mmol), N,O-dimethylhydroxylamine hydrochloride (5.77 g, 59.1 mmol), 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (11.33 g, 59.1 mmol), 4-dimethylaminopyridine (602 mg, 4.93 mmol) and triethylamine (14.96 g, 148.0 mmol) in dichloromethane (200 mL) was stirred at room temperature for 18 h. The mixture was concentrated to ca. 25 mL, then was poured into 1M hydrochloric acid (75 mL) and extracted with ethyl acetate (3×75 mL). The organic extracts were washed sequentially with 1M hydrochloric acid (50 mL), 10% (w/v) aqueous sodium carbonate (2×50 mL) and brine (50 mL), combined, dried over Na2SO4, filtered and evaporated to afford the title compound as a clear syrup (12.0 g, 44.1 mmol, 89%). 1H NMR CDCL3 : δ4.2 (brm, 2H, eq-H--C(2)), 3.72 (s, 3H, ° CH3), 3.19 (s, 3H, NCH3), 2.8 (brm, 3H, ax-H--C(2), H--C(4)), 1.7 (brm, 4H, H--C(3)), 1.46 (s, 9H, (CH3)3C).

Provenance & Evidence