Triethylamine → Tert-butyl trans-4-[(cyclopropylcarbonyl)amino]-3-hydroxypiperidine-1-carboxylate

Participants

Reaction Steps

Triethylamine (4.85 mL, 34.8 mmol) and cyclopropanecarbonyl chloride (3.18 mL, 35.0 mmol) were added to a 0° C. solution of tert-butyl trans-4-amino-3-hydroxypiperidine-1-carboxylate (7.52 g, 34.8 mmol) in tetrahydrofuran (100 mL), and the reaction was allowed to warm to room temperature and stir for 18 hours. After concentration in vacuo, the crude product was diluted with ethyl acetate, insoluble material was removed by filtration, and the solids were washed with ethyl acetate (3×50 mL). The combined filtrates were concentrated under reduced pressure, and the residue was purified by silica gel chromatography (Gradient: 0% to 5% methanol in ethyl acetate) to afford the product as a solid. Yield: 1.30 g, 4.57 mmol, 13%. LCMS m/z 285.6 [M+H]+. 1H NMR (400 MHz, CDCl3), observed peaks: δ 5.79 (br d, J=5 Hz, 1H), 4.21-4.34 (br m, 1H), 4.03-4.21 (br m, 1H), 3.70-3.79 (m, 1H), 3.34-3.42 (m, 1H), 2.66-2.79 (br m, 1H), 2.59 (br dd, J=12, 11 Hz, 1H), 1.88-1.96 (m, 1H), 1.46 (s, 9H), 1.37-1.44 (m, 1H), 1.01-1.05 (m, 2H), 0.77-0.87 (m, 2H).

Provenance & Evidence