Lithium Hydroxide → 2-[1-(Tert-butoxycarbonyl)piperidin-4-yl]propanoic acid

Participants

Reaction Steps

A mixture of 4-(1-methoxycarbonylethyl)-piperidine-1-carboxylic acid tert-butyl ester (40 g crude from last step, about 0.15 mol), LiOH (12.6 g, 0.3 mol) in water (200 mL) and THF (400 mL) was heated to reflux for 4 hours. The cooled mixture was diluted with water (200 mL) and washed with Et2O (200 mL×2). The aqueous layer was acidified with HCl (10%) at 0° C. to pH3-4. The mixture was extracted with Et2O (200 mL×3) and the combined extracts were washed with brine, dried and concentrated to give the product as a white solid (28 g, 73% from N-benzyl-4-piperidone). 1HNMR (CDCl3) δ 4.11 (m, 2H), 2.69-2.63 (m, 2H), 2.30 (p, 1H, J=7.2 Hz), 1.72-1.62 (m, 3H), 1.44 (s, 9H), 1.27-1.18 (m, 2H), 1.16 (d, 3H, J=7.2 Hz).

Provenance & Evidence