反应详情

温度

-68 °C

To a −70° C. solution of LiHMDS in THF (1M, 6.97 L, 6.97 mol) was added a solution of the product of Step B (763.5 g, 3.16 mol) in THF (800 mL) over a 2 h period while keeping the temperature at or below −68° C. The resulting solution was stirred for 45 min at −68° C. A solution of the product of Step C (1.267 kg, 4.426 mol) in THF (800 mL) was added over 1 h 50 min period while maintaining a temperature of ˜−66° C. The reaction was stirred at ˜-66° C. for 45 min. The reaction was warmed to −15° C. and worked up by addition to mixture of aqueous HCl and ice. The mixture was extracted with toluene, the organic layer was washed with water, brine and dried over MgSO4. The organic layer was concentrated and purified on silica gel using a mixture of EtOAc in heptanes to provide the product of Step D as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) d=5.69-5.86 (m, 2H), 4.79-4.93 (m, 1H), 4.68-4.80 (m, 1H), 3.67 (s, 3H), 3.53-3.62 (m, 2H), 2.16-2.30 (m, 1H), 2.04-2.16 (m, 2H), 1.70-1.81 (m, 1H), 1.41 (s, 9H), 0.78-0.91 (m, 13H), 0.00 (s, 6H).

1. custombelow −68° C
2. temperaturewhile maintaining a temperature of ˜−66° C
3. stirringThe reaction was stirred at ˜-66° C. for 45 min
4. temperatureThe reaction was warmed to −15° C.
5. extractionThe mixture was extracted with toluene
6. washthe organic layer was washed with water, brine
7. dry with materialdried over MgSO4
8. concentrationThe organic layer was concentrated
9. custompurified on silica gel using
10. additiona mixture of EtOAc in heptanes