Acetic Acid → Tert-butyl 3-(3-fluoroazetidin-1-yl)azetidine-1-carboxylate

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-[1,31biazetidinyl-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, 1H); 3.93 (dd, J=9.1, 7.0 Hz, 2H); 3.74-3.59 (m, 4H); 3.45-3.38 (m, 1H); 3.31-3.25 (m, 1H); 3.23-3.17 (m, 1H); 1.43 (s, 9H).

1. stirringthe reaction mixture was stirred for 18 h at room temperature
2. customThe reaction mixture was partitioned between DCM and water
3. washthe organic phase was washed with brine
4. dry with materialdried over sodium sulphate
5. concentrationconcentrated
6. customThe residue was purified by flash chromatography (Si—PPC, EtOAc:cyclohexane, gradient 40:60 to 100:0)

ORD record

ord-a60faffb587a4b67879a2858e1c12cbf

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08173650B2