反应详情

Under nitrogen, MeMgBr solution (2.9 M in 2-methyltetrahydrofuran solution, 3.06 L, 8.88 mol) was diluted by adding into THF (8 L) at 0-5° C. A solution of 6-bromo-3,3-bis(hydroxymethyl)-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one (700 g, 2.22 mol) in THF (5 L) was added dropwise via a dropping funnel to the diluted MeMgBr solution maintaining the temperature below 5° C. After the addition was complete, the reaction mixture was allowed to warm to room temperature and stirred for 30 minutes. Then the reaction mixture was heated under reflux overnight. The mixture was cooled to room temperature followed by cooling with an ice-water bath and 6 M hydrochloric acid (3.7 L, 22.2 mol) was added dropwise via a dropping funnel over 30 minutes maintaining the temperature below 10° C. After the addition was complete, the mixture was allowed to warm to room temperature and stirred for 20 minutes. The mixture was extracted with toluene (5 L×2) and the combined extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was treated with a mixture of hexane/toluene (5:1, 2 L) and the resulting suspension was stirred for 30 minutes. The precipitate was collected by filtration, washed with hexane and dried under vacuum to give (6-bromo-2,2-dimethyl-4-methylene-3,4-dihydro-2H-chromene-3,3-diyl)dimethanol (500 g).

1. temperaturemaintaining the temperature below 5° C
2. additionAfter the addition
3. temperatureThen the reaction mixture was heated
4. temperatureunder reflux overnight
5. temperatureThe mixture was cooled to room temperature
6. temperatureby cooling with an ice-water bath
7. temperaturemaintaining the temperature below 10° C
8. additionAfter the addition
9. temperatureto warm to room temperature
10. stirringstirred for 20 minutes
11. extractionThe mixture was extracted with toluene (5 L×2)
12. washthe combined extracts were washed with brine
13. dry with materialdried over Na2SO4
14. concentrationconcentrated under reduced pressure
15. additionThe residue was treated with a mixture of hexane/toluene (5:1, 2 L)
16. stirringthe resulting suspension was stirred for 30 minutes
17. filtrationThe precipitate was collected by filtration
18. washwashed with hexane
19. customdried under vacuum