反应详情

To a solution of N-(3-{3-[3-(4-fluorophenyl)propanoyl]-6-methyl-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide (Preparation 118, 86 mg, 0.21 mmol) in anhydrous tetrahydrofuran (2 ml) under a nitrogen atmosphere at 0° C. was added dropwise lithium aluminium hydride (1.0M solution in tetrahydrofuran, 0.42 ml, 0.42 mmol) and the mixture was stirred at room temperature for 3 h. The rapidly stirred reaction mixture was treated sequentially with water (0.42 ml), sodium hydrogen carbonate (400 mg) and ethyl acetate (10 ml). After 30 min the reaction mixture was filtered and concentrated in vacuo to afford a colourless oil. The oil was purified by preparative HPLC (condition 8) to give a pale yellow oil which was partitioned between dichloromethane (10 ml) and aqueous potassium carbonate solution (4% w:v, 5 ml). The layers were separated and the organic layer was washed with water (3 ml), dried (Na2SO4), filtered and concentrated in vacuo to afford the title compound as a colourless oil (52 mg, 62%). The free base (45 mg, 0.112 mmol) was dissolved in anhydrous diethyl ether (5 ml) and dichloromethane (1 ml) and the solution was treated with hydrogen chloride (1.0M solution in diethyl ether, 0.123 ml). The heterogeneous suspension was concentrated in vacuo to afford the hydrochloride salt of the title compound as a white solid (46 mg, 94%).

1. customThe rapidly stirred reaction mixture
2. filtrationAfter 30 min the reaction mixture was filtered
3. concentrationconcentrated in vacuo
4. customto afford a colourless oil
5. customThe oil was purified by preparative HPLC (condition 8)
6. customto give a pale yellow oil which
7. customwas partitioned between dichloromethane (10 ml) and aqueous potassium carbonate solution (4% w:v, 5 ml)
8. customThe layers were separated
9. washthe organic layer was washed with water (3 ml)
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated in vacuo