3,5-Bis(trifluoromethyl)benzoic acid → 1-tert-Butoxycarbonyl-4-phenyl-4-[3,5-bis(trifluoromethyl) benzoyloxymethyl]piperidine

Participants

Reaction Steps

1-(3-Dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (897 mg) was added to a stirred solution of 3,5-bis(trifluoromethyl) benzoic acid (292 mg) and 4-dimethylaminopyridine (483 mg) in dry dimethylformamide (20 ml). The resulting solution was stirred for 30 minutes then the compound of step (a) above (1.0 g) was added. The resulting solution was stirred at room temperature for 19 hours. At this time the reaction was diluted with water (200 ml) and extracted into ethyl acetate. The organic layers were separated, washed with water, brine, and dried over MgSO4. Filtration and removal of solvent under reduced pressure afforded a yellow oil. Purification by chromatography on silica gel (20% ethyl acetate/n-hexane) afforded the product as a clear oil. 1H NMR (360 MHz, CDCl3) δ 1.4 (9H, s), 1.95 (2H, m), 2.3 (2H, m), 3.03 (2H, m), 3.8 (2H, m), 4.35 (2H, s), 7.0-7.2 (5H, m), 8.01 (1H, s), 8.25 (2H, s).

Provenance & Evidence