反应详情

(1R*,2R*,5R*)-2-{[3,5-Bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octane (Example 60; 345 mg, 0.80 mmol) was dissolved in dimethylformamide (3 ml) and potassium carbonate (331 mg, 2.40 mmol) added. This was stirred for 5 minutes at room temperature then 2-bromoethanol (0.086 ml, 1.21 mmol) added and the reaction mixture heated for 5 days at 60° C. Only a small amount of starting material had converted to product so a further 25 equivalents of 2-bromoethanol (1.42 ml, 20 mmol) was added and the temperature increased to 80° C. overnight. The reaction mixture was poured into 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%-20% ethyl acetate in iso-hexane] to give a yellow oil and the hydrochloride salt was made by adding 1 equivalent of hydrogen chloride in diethyl ether (1N). The title compound was filtered off and dried at 60° C. in vacuo.

1. temperaturethe reaction mixture heated for 5 days at 60° C
2. additionwas added
3. temperaturethe temperature increased to 80° C. overnight
4. extractionextracted with ethyl acetate (×3)
5. dry with materialdried (MgSO4)
6. concentrationconcentrated in vacuo
7. customto give a brown oil
8. customThis was purified by flash column chromatography [5%-20% ethyl acetate in iso-hexane]
9. customto give a yellow oil
10. filtrationThe title compound was filtered off
11. customdried at 60° C. in vacuo