反应详情

To ethyl 7-(4-(6-bromopyridin-2-ylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate (Example 52, Step A, 0.021 g, 0.039 mmol) in THF (0.5 ml) was added 0.5 isobutylzinc bromide in THF (0.12 ml, 0.059 mmol) followed by bis(tri-t-butylphosphine)palladium (0) (0.0010 g, 0.0020 mmol) and the reaction was stirred at ambient temperature for 1 hour. The reaction was loaded onto silica gel and the product eluted using 3:1 hexanes/ethyl acetate. The resulting oil was dissolved in THF/MeOH/1N NaOH (0.5 ml/0.5 ml/0.25 ml) and stirred at ambient temperature for 3 hours. The reaction was diluted with DCM (35 ml) and washed with water with made acidic (pH=5) with 1N HCl. The organic layer was washed with brine (10 ml), dried over magnesium sulfate and concentrated to give the title compound (0.013 g, 0.027 mmol, 68% yield) as a white solid. MS (ESI) m/z=481.31 (M+H).

1. washthe product eluted
2. dissolutionThe resulting oil was dissolved in THF/MeOH/1N NaOH (0.5 ml/0.5 ml/0.25 ml)
3. stirringstirred at ambient temperature for 3 hours
4. additionThe reaction was diluted with DCM (35 ml)
5. washwashed with water with made acidic (pH=5) with 1N HCl
6. washThe organic layer was washed with brine (10 ml)
7. dry with materialdried over magnesium sulfate
8. concentrationconcentrated