反应详情

To a solution of 4-bromo-1-chloro-2-(4-(2-cyclobutoxyethoxy)benzyl)benzene (110 mg, 0.3 mmol) in anhydrous toluene/tetrahydrofuran (v/v=2/1, 2 mL) was added n-BuLi (0.17 mL, 2.5 M) dropwise at −78° C. The mixture was stirred for 30 min and then transferred to a solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)tetrahydro-2H-pyran-2-one (195 mg, 0.4 mmol) in anhydrous toluene (1 mL) at −78° C. The mixture was stirred at −78° C. for 2 h until starting material was consumed. The reaction was quenched with methanesulfonic acid (54 μL in 1.4 mL methanol), and the mixture was allowed to warm to room temperature and stirred overnight. Then water was added, the organic phase was separated, and the water phase was extracted with ethyl acetate. The organic phases were combined, washed with saturated sodium bicarbonate, then with water and then with brine, and then dried over anhydrous sodium sulfate, filtered and concentrated to get the crude product. The crude product was dissolved in acetonitrile/dichloromethane (1.2 mL), triethylsilane (0.3 mL, 1.9 mmol) was added, the mixture was cooled to −40° C., and boron trifluoride diethyl etherate (1.8 μL, 1.4 mmol) was added quickly. After addition, the mixture was stirred for 2 h at 0° C. The reaction was quenched with saturated aqueous sodium bicarbonate. The volatiles were removed under reduced pressure and the residue was extracted with ethyl acetate, washed with water and then with brine, and then dried over anhydrous sodium sulfate. The residue was filtered, concentrated, and purified by preparative LC-MS to obtain 16 mg of pure product. 1H NMR (CD3OD, 400 MHz): δ 7.25-7.34 (m, 3H), 7.09-7.11 (m, 2H), 6.81-6.83 (m, 2H), 4.01-4.09 (m, 6H), 3.85-3.88 (m, 1H), 3.65-3.70 (m, 3H), 3.37-3.44 (m, 3H), 3.26-3.28 (m, 1H), 2.18-2.23 (m, 2H), 1.90-1.95 (m, 2H), 1.55-1.72 (m, 1H), 1.48-1.53 (m, 1H); MS ES− (m/z): 523 (M+45)−; MS ES+ (m/z): 479 (M+1)+, 496 (M+18)+.

1. stirringThe mixture was stirred at −78° C. for 2 h
2. customwas consumed
3. customThe reaction was quenched with methanesulfonic acid (54 μL in 1.4 mL methanol)
4. stirringstirred overnight
5. additionThen water was added
6. customthe organic phase was separated
7. extractionthe water phase was extracted with ethyl acetate
8. washwashed with saturated sodium bicarbonate
9. dry with materialwith water and then with brine, and then dried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customto get the crude product
13. temperaturethe mixture was cooled to −40° C.
14. additionAfter addition
15. stirringthe mixture was stirred for 2 h at 0° C
16. customThe reaction was quenched with saturated aqueous sodium bicarbonate
17. customThe volatiles were removed under reduced pressure
18. extractionthe residue was extracted with ethyl acetate
19. washwashed with water
20. dry with materialwith brine, and then dried over anhydrous sodium sulfate
21. filtrationThe residue was filtered
22. concentrationconcentrated
23. custompurified by preparative LC-MS