Ammonium Chloride → tert-butyl 3-hydroxy-3-(trifluoroMethyl)azetidine-1-carboxylate

To a stirred solution of tert-butyl 3-oxoazetidine-1-carboxylate (0.50 g, 2.9 mmol) and (trifluoromethyl)trimethylsilane (0.65 mL, 4.4 mmol) in tetrahydrofuran (5 mL) at 0° C. was added tetramethylammonium fluoride (0.014 g, 0.15 mmol). The reaction mixture was warmed to room temperature. After 1 h, the reaction mixture was poured into a 0.5M aqueous ammonium chloride solution (25 mL) and extracted with diethyl ether (25 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated to a crude oil. The crude oil was dissolved in tetrahydrofuran (5 mL). A 1M aqueous citric acid solution (5 mL) was added and the mixture was stirred for 1 h. The reaction mixture was partitioned between diethyl ether (25 mL) and water (10 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated to a crude oil. The residue was purified by silica gel chromatography (EtOAc/Hexanes gradient) to afford tert-butyl 3-hydroxy-3-(trifluoromethyl)azetidine-1-carboxylate as a white solid. 1H NMR (600 MHz, DMSO-D6) 4.17 (d, 2H); 3.91 (d, 2H); 1.43 (s, 9H).

1. extractionextracted with diethyl ether (25 mL)
2. dry with materialThe organic layer was dried over magnesium sulfate
3. filtrationfiltered
4. concentrationconcentrated to a crude oil
5. dissolutionThe crude oil was dissolved in tetrahydrofuran (5 mL)
6. additionA 1M aqueous citric acid solution (5 mL) was added
7. customThe reaction mixture was partitioned between diethyl ether (25 mL) and water (10 mL)
8. dry with materialThe organic layer was dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated to a crude oil
11. customThe residue was purified by silica gel chromatography (EtOAc/Hexanes gradient)

ORD record

ord-8365fda449ab46cca23c91986096385b

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08183245B2