Acetic Acid → Tert-butyl 3-(3-fluoroazetidin-1-yl)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 (0.14 g, 0.82 mmol), 3-fluoroazetidine hydrochloride (0.1 g, 0.9 mmol) in DCE (3 mL), trimethoxymethane (0.88 mL, 8.5 mmol) and acetic acid (0.046 mL, 0.81 mmol). The reaction mixture was stirred for 3 h at room temperature. Sodium triacetoxyborohydride (0.26 g, 1.22 mmol) was added and the reaction mixture was stirred for 18 h at room temperature. The reaction mixture was partitioned between DCM and water; the organic phase was washed with brine, dried over sodium sulphate and concentrated. The residue was purified by flash chromatography (Si—PPC, EtOAc:cyclohexane, gradient 40:60 to 100:0) to give 3-Fluoro-[1,3]biazetidinyl-1′-carboxylic acid tert-butyl ester as a colourless oil (0.109 g, 59%). 1H NMR (CDCl3, 400 MHz) δ 5.15 (dt, J=57.1, 5.3 Hz, 1 H); 3.93 (dd, J=9.1, 7.0 Hz, 2 H); 3.74-3.59 (m, 4 H); 3.45-3.38 (m, 1 H); 3.31-3.25 (m, 1 H); 3.23-3.17 (m, 1 H); 1.43 (s, 9 H).

Provenance & Evidence