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-[1,3]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).

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-37a71594659a4b64b94cdbfe1dcbf66e

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08394796B2