反应详情

To a solution of 2-(4,4-dimethylcyclohex-2-enyl)isoindoline-1,3-dione (11.59 g, 45.4 mmol) in chloroform (110 mL) and ethanol (3.83 mL) was added N-bromosuccinimide (10.34 g, 58.1 mmol) as a solid over a few min at ambient temperature. After addition was complete, the reaction mixture was stirred at ambient temperature overnight under nitrogen. The reaction mixture was washed with 1 M aqueous solution of sodium thiosulfate (100 mL). The aqueous layer was extracted with chloroform (100 mL) and the combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated to an oil. To this oil was added 150 mL THF (150 mL) and a 1N aqueous solution of hydrochloric acid (30 mL). The resulting mixture was stirred at ambient temperature for 2 h. The THF was removed under reduced pressure and the remaining aqueous layer was diluted with ethyl acetate (150 mL) and 75 mL of a 1:1 water:saturated aqueous sodium bicarbonate solution mixture. The layers were separated and the aqueous was back-extracted aqueous with ethyl acetate (75 mL). The combined ethyl acetate layers were washed with brine (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated to an oil that was purified by silica gel chromatography (0-25% ethyl acetate/hexane) to afford a mixture of 2-((1R,2S,3S)-2-bromo-3-hydroxy-4,4-dimethylcyclohexyl)isoindoline-1,3-dione, 2-((1S,2R,3R)-2-bromo-3-hydroxy-4,4-dimethylcyclohexyl)isoindoline-1,3-dione, 2-((1R,2R,3R)-3-bromo-2-hydroxy-4,4-dimethylcyclohexyl)isoindoline-1,3-dione, and 2-((1S,2S,3S)-3-bromo-2-hydroxy-4,4-dimethylcyclohexyl)isoindoline-1,3-dione (11.4 g, 32.4 mmol, 71.3% yield). MS (ESI) m/z 374.5 [M+1]+ and 376.5 [M+1]+.

1. additionAfter addition
2. washThe reaction mixture was washed with 1 M aqueous solution of sodium thiosulfate (100 mL)
3. extractionThe aqueous layer was extracted with chloroform (100 mL)
4. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated to an oil
7. additionTo this oil was added 150 mL THF (150 mL)
8. stirringThe resulting mixture was stirred at ambient temperature for 2 h
9. customThe THF was removed under reduced pressure
10. additionthe remaining aqueous layer was diluted with ethyl acetate (150 mL) and 75 mL of a 1:1 water
11. customThe layers were separated
12. extractionthe aqueous was back-extracted aqueous with ethyl acetate (75 mL)
13. washThe combined ethyl acetate layers were washed with brine (50 mL)
14. dry with materialdried over anhydrous magnesium sulfate
15. filtrationfiltered
16. concentrationconcentrated to an oil that
17. customwas purified by silica gel chromatography (0-25% ethyl acetate/hexane)
18. customto afford