Water → 3-(2,3-Difluorophenyl)-1-ethylazetidin-3-ol

Temperature

120 °C

1,3-dichloro-2-(2,3-difluorophenyl)propan-2-ol (6.0 g, 24.89 mmol) was dissolved in acetonitrile (90 ml) and transferred to 6 different microwave vials where each vial contained equal amounts (1.0 g, 2.49 mmol). In each tube sodium bicarbonate (1.04 g, 12.44 mmol (in total 6.27 g, 74.67 mmol)) was added and the tubes were sealed. Through the septum ethylamine in tetrahydrofurane (2.0 M, 2.07 ml, 4.15 mmol (in total 12.44 ml, 24.89 mmol) was added and the mixture was heated at 120° C. for 30 min under microwave irradiation. Additional ethylamine in tetrahydrofurane (2.0 M, 1.03 ml, 2.07 mmol (in total 6.22 ml, 12.44 mmol) was added and the mixture was heated at 120° C. for 30 min under microwave irradiation. The solutions where pooled, water (100 ml) and tert-butyl methyl ether (100 ml) was added and the organic phase was collected. The aqueous phase was extracted with tert-butyl methyl ether (100 ml), the pooled organic phase was dried (Na2SO4) and evaporated. The crude product was purified by flash column chromatography on silica gel (ethyl acetate/methanol, 1:0 to 9:1) to give the title compound (2.53 g, 48%). The amine was converted to the fumaric acid salt and recrystallized from ethanol/diethyl ether/diisopropyl ether: M.p. 148-150° C. MS m/z (relative intensity, 70 eV) 213 (M+, 1), 156 (39), 141 (75), 127 (56), 58 (bp).

1. customthe tubes were sealed
2. temperaturethe mixture was heated at 120° C. for 30 min under microwave irradiation
3. customthe organic phase was collected
4. extractionThe aqueous phase was extracted with tert-butyl methyl ether (100 ml)
5. dry with materialthe pooled organic phase was dried (Na2SO4)
6. customevaporated
7. customThe crude product was purified by flash column chromatography on silica gel (ethyl acetate/methanol, 1:0 to 9:1)

ORD record

ord-d8c131e50e714c4bb9caeb80d5f0c514

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08586572B2