反应详情

1,2,4-Triazole (25 mg, 0.37 mmol) was dissolved in acetonitrile (2 ml) and sodium hydroxide (44 mg, 1.11 mmol). This was stirred at room temperature for 30 minutes then tetrabutylammonium hydrogen sulphate and (1R*,2R*,5R*)-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-8-(2-mesyloxyethyl)-1-phenyl-8-azabicyclo[3.2.1]octane (Example 68; 201 mg, 0.37 mmol) added. The reaction was heated to reflux for 2.5 hours. The reaction mixture was diluted with water and extracted with ethyl acetate (×3), dried (MgSO4), and concentrated in vacuo to give a brown oil. This was purified by flash column chromatography [5% methanol in dichloromethane] to give a brown oil and the hydrochloride salt was made by adding 1 equivalent of hydrogen chloride in diethyl ether (1N) and the title compound filtered off and dried in vacuo at 60° C.

1. temperatureThe reaction was heated
2. temperatureto reflux for 2.5 hours
3. extractionextracted with ethyl acetate (×3)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated in vacuo
6. customto give a brown oil
7. customThis was purified by flash column chromatography [5% methanol in dichloromethane]
8. customto give a brown oil
9. filtrationthe title compound filtered off
10. customdried in vacuo at 60° C.