反应详情

温度

-78 °C

To a −78° C. solution of 37.3 mL (266 mmol) of diisopropylamine in dry, degassed THF (150 mL) was added 100 mL (250 mmol) of a degassed 2.5 M solution of n-butyllithium in hexanes slowly via cannula. The light yellow solution was stirred at −78° C. for 15 min, then was warmed to 0° C. and stirred for an additional 5 min. To the ice-cooled LDA solution was added a solution of 85.7 g (133 mmol) of (5R,6S)-1-((S)-1-(tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methylpiperidin-2-one (Example 185, Step D) in dry, degassed THF (210 mL) via cannula over a 15 min period. The dark orange solution was stirred at 0° C. for 30 min and then 34.5 mL (399 mmol) of allyl bromide was added quickly via syringe. After 20 sec, the ice bath was removed and the reaction was placed in a room temperature water bath and stirred for an additional 15 min. The reaction was quenched with saturated aq. ammonium chloride, and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by chromatography on silica gel (Biotage® Snap™ column; Biotage, LLC, Charlotte, N.C.), 6-14% EtOAc/hexanes, gradient elution) provided the title compound as a white foam.

1. customdegassed THF (150 mL)
2. additionwas added 100 mL (250 mmol) of a degassed 2.5 M solution of n-butyllithium in hexanes slowly via cannula
3. temperaturewas warmed to 0° C.
4. stirringstirred for an additional 5 min
5. temperatureTo the ice-cooled LDA solution
6. customin dry
7. customdegassed THF (210 mL) via cannula over a 15 min period
8. stirringThe dark orange solution was stirred at 0° C. for 30 min
9. waitAfter 20 sec
10. customthe ice bath was removed
11. customwas placed in a room temperature
12. stirringstirred for an additional 15 min
13. customThe reaction was quenched with saturated aq. ammonium chloride
14. extractionextracted with EtOAc (3×)
15. dry with materialThe combined organic layers were dried over Na2SO4
16. filtrationfiltered
17. concentrationthe filtrate was concentrated
18. customPurification of the residue by chromatography
19. washon silica gel (Biotage® Snap™ column; Biotage, LLC, Charlotte, N.C.), 6-14% EtOAc/hexanes, gradient elution)