3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → tert-Butyl 3-(4,4-difluoro-1-piperidyl)azetidine-1-carboxylate

Participants

Reaction Steps

A 10 mL round-bottomed flask was charged with a solution of 3-oxoazetidine-1-carboxylic acid tert-butyl ester (0.51 g, 3 mmol), 4,4-difluoropiperidine hydrochloride (0.71 g, 4.5 mmol) and 4 Å molecular sieves (0.8 g) in DCE (8 mL). The reaction mixture was stirred for 7 h at room temperature. Sodium triacetoxyborohydride (1.27 g, 6 mmol) was added and the reaction mixture was stirred for 18 h at room temperature. The suspension was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (Si—PPC, EtOAc: cyclohexane, gradient 0:100 to 75:25) to give 3-(4,4-Difluoropiperidin-1-yl)azetidine-1-carboxylic acid tert-butyl ester as a yellow oil (0.69 g, 83%). 1H NMR (CDCl3, 400 MHz) δ 3.94 (dd, J=8.7, 7.1 Hz, 2 H); 3.78 (dd, J=8.7, 5.3 Hz, 2 H); 3.17-3.10 (m, 1 H); 2.45-2.41 (m, 4 H); 2.10-1.94 (m, 4 H); 1.43 (s, 9 H).

Provenance & Evidence