反应详情

温度

85 °C

A solution of racemic 2-{2-[5-fluoro-2-(methyloxy)phenyl]-2-methylpropyl}-2-(trifluoromethyl)oxirane (which may be prepared according to WO 04/063163, 350 mg, 1.2 mmol), in acetonitrile (2 mL) was added to a mixture of phenylmethyl 3-(4-amino-6-methyl-1H-indazol-1-yl)benzoate (357 mg, 1.0 mmol) and ytterbium(III) triflate (124 mg, 0.2 mmol). The mixture was stirred and heated to 85° C. under nitrogen in a greenhouse apparatus for 18 hours when the temperature was raised to 100° C. and the mixture heated under vigorous reflux for a further ˜21 hours. The mixture was cooled to room temperature and partitioned between dichloromethane (50 mL) and aqueous sodium bicarbonate (50 mL). The aqueous layer was extracted again with dichloromethane (50 mL) and the combined organic extracts were dried over anhydrous sodium sulphate and evaporated. The residue was purified by silica gel chromatography using the Flashmaster II (50 g cartridge) eluting with a cyclohexane to 1:1 cyclohexane:ethyl acetate gradient over 40 minutes to give the title compound as a white solid (424 mg).

1. temperaturewas raised to 100° C.
2. temperaturethe mixture heated
3. temperatureunder vigorous reflux for a further ˜21 hours
4. temperatureThe mixture was cooled to room temperature
5. custompartitioned between dichloromethane (50 mL) and aqueous sodium bicarbonate (50 mL)
6. extractionThe aqueous layer was extracted again with dichloromethane (50 mL)
7. dry with materialthe combined organic extracts were dried over anhydrous sodium sulphate
8. customevaporated
9. customThe residue was purified by silica gel chromatography
10. washeluting with a cyclohexane to 1:1 cyclohexane