反应详情

To a solution of 136 mg (0.258 mmol) of 3'-bromo-4'-t-butyldiphenylsilyloxymethyl-1,1'-biphenyl-2-nitrile (Step G) in 3 mL of dry methylene chloride under a nitrogen atmosphere was added 199 mg (0.775 mmol) of tetra-n-butylammonium borohydride. The reaction mixture was heated at reflux for 8 hours, cooled to room temperature, poured into 25 mL of water and extracted with ethyl acetate (3×35 mL). The combined organic extracts were washed with water (25 mL), saturated aqueous sodium bicarbonate (25 mL) and brine (25 mL). The organic layer was dried over magnesium sulfate, filtered and the solvent removed under vacuum to give an oil which was dissolved in 3 mL of tetrahydrofuran and treated with 1 mL of 6 N aqueous hydrochloric acid. The resulting solution was heated at reflux for 4 hours, cooled in an ice bath and quenched with 10 mL of 1 N aqueous sodium hydroxide. The mixture was extracted with ethyl acetate (3×35 mL). The organic extracts were washed with water (25 mL), saturated aqueous sodium bicarbonate (25 mL) and brine (25 mL). The organic layer was dried over sodium sulfate, filtered and the solvent removed under vacuum to give an oil which was purified by flash column chromatography on silica gel, eluting with chloroformB 10% ammonium hydroxide (33%) in methanol (9:1), to afford 43 mg (57%) of the product as an off-white solid. 1H NMR (200 MHz, CD3OD): δ 3.69 (s, 2H), 4.68 (s, 2H), 7.16 (dd; 7, 6 Hz; 1H), 7.21-7.41 (m, 4H), 7.47 (dd; 9, 8 Hz; 1H), 7.58 (d, 8 Hz, 1H). FAB-MS: calculated for C14H14BrNO 292; found 292, 293 (50%).

1. temperatureThe reaction mixture was heated
2. temperatureat reflux for 8 hours
3. extractionextracted with ethyl acetate (3×35 mL)
4. washThe combined organic extracts were washed with water (25 mL), saturated aqueous sodium bicarbonate (25 mL) and brine (25 mL)
5. dry with materialThe organic layer was dried over magnesium sulfate
6. filtrationfiltered
7. customthe solvent removed under vacuum
8. customto give an oil which
9. temperatureThe resulting solution was heated
10. temperatureat reflux for 4 hours
11. temperaturecooled in an ice bath
12. customquenched with 10 mL of 1 N aqueous sodium hydroxide
13. extractionThe mixture was extracted with ethyl acetate (3×35 mL)
14. washThe organic extracts were washed with water (25 mL), saturated aqueous sodium bicarbonate (25 mL) and brine (25 mL)
15. dry with materialThe organic layer was dried over sodium sulfate
16. filtrationfiltered
17. customthe solvent removed under vacuum
18. customto give an oil which
19. customwas purified by flash column chromatography on silica gel
20. washeluting with chloroformB 10% ammonium hydroxide (33%) in methanol (9:1)