反应详情

To a solution of (S)-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-(2,3,4,5,7,8,9,10-octahydro-1H-naphtho[2,3-b]azepin-5-yl)-amine (Example 77, Step 3) (0.19 mmol) in dichloromethane (5 mL), add sodium bicarbonate (0.28 mmol) and methanol (2 mL). Add a 1.0 M solution of iodine monochloride (0.28 mmol) in dichloromethane dropwise. After stirring for 1 h at room temperature, quench the reaction with concentrated aqueous sodium metabisulfite. Dilute with dichloromethane (20 mL) and water (20 mL). Separate the organic phase and wash the aqueous with dichloromethane (2×10 mL). Dry the combined organics over sodium sulfate, filter, and remove solvent under vacuum. Dissolve the crude intermediate in dioxane (5 mL) and purge with nitrogen. To this solution add palladium acetate (0.04 mmol), diphenylphosphinoferrocene (0.04 mmol), cesium fluoride (0.76 mmol), and methylboronic acid (0.76 mmol). Heat the mixture at 60° C. for 4 h, then cool to room temperature and remove the solvent under vacuum. Chromatograph the product over silica gel eluting with ethyl acetate/hexane (5-25%) to afford the title compound. MS (ES+): 539 (M+H).

1. customquench
2. customthe reaction with concentrated aqueous sodium metabisulfite
3. customSeparate the organic phase
4. washwash the aqueous with dichloromethane (2×10 mL)
5. dry with materialDry the combined organics over sodium sulfate
6. filtrationfilter
7. customremove solvent under vacuum
8. dissolutionDissolve the crude intermediate in dioxane (5 mL)
9. custompurge with nitrogen
10. temperatureHeat the mixture at 60° C. for 4 h
11. temperaturecool to room temperature
12. customremove the solvent under vacuum