反应详情

(1R*,2R*,5S*,6R*)-6-Acetamidoazido-8-benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octane (Example 104; 240 mg, 0.40 mmol) was dissolved in ethyl acetate (10 ml) and glacial acetic acid (1 ml) then 10% palladium hydroxide (30 mg) added and the mixture hydrogenated at 45 psi overnight. The reaction mixture was then filtered and the mixture further hydrogenated with fresh catalyst (30 mg) overnight. The reaction mixture was filtered then concentrated in vacuo, basified (saturated sodium hydrogen carbonate solution), extracted with dichloromethane (×3), dried (MgSO4), and concentrated in vacuo. The crude product was purified by flash column chromatography [10% methanol in dichloromethane] to give an oil which when concentrated with iso-hexane gave a white solid. The hydrochloride salt was made by dissolving in diethyl ether and adding 1 equivalent of hydrogen chloride in diethyl ether. The title compound was filtered off and dried in vacuo at 60° C.

1. customhydrogenated at 45 psi overnight
2. filtrationThe reaction mixture was then filtered
3. customfurther hydrogenated with fresh catalyst (30 mg) overnight
4. filtrationThe reaction mixture was filtered
5. concentrationthen concentrated in vacuo
6. extractionextracted with dichloromethane (×3)
7. dry with materialdried (MgSO4)
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by flash column chromatography [10% methanol in dichloromethane]
10. customto give an oil which when
11. concentrationconcentrated with iso-hexane
12. customgave a white solid
13. filtrationThe title compound was filtered off
14. customdried in vacuo at 60° C.