反应详情

To a solution of 4-bromo-1-chloro-2-(4-ethoxy-benzyl)-benzene (10.0 g, 30.71 mmol) in dichloromethane (40.0 mL) cooled to 0 degrees Celsius under nitrogen was added drop-wise over 30 minutes a 1M solution of boron trichloride in dichloromethane (34 mL, 34.0 mmol). After the addition was complete, the reaction was allowed to warm to room temperature overnight (˜16 hours). The reaction mixture was cooled to 0 degrees Celsius and an aqueous solution of 1N hydrochloric acid was added. The resulting mixture was stirred for 30 minutes and then extracted using dichloromethane. The organic layer was separated and the aqueous layer was extracted two times with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The TLC showed only 50% conversion. The crude material was redissolved in dichloromethane (40 mL), cooled to 0 degrees Celsius, and a 1M solution of boron tribromide in dichloromethane (31 mL, 31 mmol) was added dropwise. The reaction mixture was allowed to warm to room temperature over the weekend (˜55 hours). The reaction mixture was cooled to 0 degrees Celsius and an aqueous solution of 1N hydrochloric acid was added dropwise. The resulting mixture was stirred for 30 minutes and then extracted using dichloromethane. The organic layer was separated and the aqueous layer was extracted two times with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The reaction was purified by flash chromatography over silica gel using the ISCO automated chromatography unit (120 g silica gel column) and eluting with a gradient of 0 to 100% ethyl acetate in heptane. 9 g (98% yield) of the desired product obtained as a white solid.

1. additionAfter the addition
2. temperatureThe reaction mixture was cooled to 0 degrees Celsius
3. extractionextracted
4. customThe organic layer was separated
5. extractionthe aqueous layer was extracted two times with dichloromethane
6. dry with materialThe combined organic layers were dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. dissolutionThe crude material was redissolved in dichloromethane (40 mL)
10. temperaturecooled to 0 degrees Celsius
11. temperatureto warm to room temperature over the weekend (˜55 hours)
12. temperatureThe reaction mixture was cooled to 0 degrees Celsius
13. stirringThe resulting mixture was stirred for 30 minutes
14. extractionextracted
15. customThe organic layer was separated
16. extractionthe aqueous layer was extracted two times with dichloromethane
17. dry with materialThe combined organic layers were dried over magnesium sulfate
18. filtrationfiltered
19. concentrationconcentrated under reduced pressure
20. customThe reaction was purified by flash chromatography over silica gel using the ISCO automated chromatography unit (120 g silica gel column)
21. washeluting with a gradient of 0 to 100% ethyl acetate in heptane