tert-Butyl 4-oxopiperidine-1-carboxylate → tert-Butyl 4-(3,3-difluoroazetidin-1-yl)piperidine-1-carboxylate

Participants

Reaction Steps

A 10 mL round-bottomed flask was charged with a solution of 4-oxopiperidine-1-carboxylic acid tert-butyl ester (0.4 g, 0.20 mmol), 3,3-difluoroazetidine hydrochloride (0.31 g, 0.24 mmol) and 4 Å molecular sieves (2.4 g) in DCE (10 mL). The reaction mixture was stirred for 3 h at room temperature. Sodium triacetoxyborohydride (0.85 g, 4.01 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 to give 4-(3,3-Difluoroazetidin-1-yl)piperidine-1-carboxylic acid tert-butyl ester as a colourless oil (0.53 g, 96%). 1H NMR (300 MHz, CDCl3): δ 3.94-3.90 (m, 2 H), 3.57 (t, J=11.9 Hz, 4 H), 2.96-2.81 (m, 2 H), 2.34-2.23 (m, 1 H), 1.71-1.58 (m, 2 H), 1.45 (s, 9 H), 1.35-1.21 (m, 2 H).

Provenance & Evidence