反应详情

A mixture of 24 (3.0 g, 10 mmol, 1.0 equiv), o-anisidine (1.3 g, 1.2 mL, 100 mmol, 1.0 equiv), toluene (45 mL) containing a crystal of p-toluenesulfonic was refluxed for 5.5 hr with H2O removal (Dean-Stark trap). The mixture was cooled to room temperature and stirred overnight. The mixture was concentrated under reduced pressure to give crude imine 25 as a yellow-brown oil. Crude 25 was dissolved in THF (75 mL) and the solution cooled to −2° C. 1.8M phenyllithium in di-n-butylether (15 mL, 27 mmol, 2.7 equiv) was added dropwise via syringe at −2° C. to 0° C. The yellow-brown solution was allowed to warm to room temperature and stirred 1.5 hr. The mixture was cooled to ˜10° C., quenched by the slow, dropwise addition of saturated NH4Cl solution (20 mL) then partitioned between 1:1 EtOAc heptanes (150 mL) and H2O (25 mL). The organic phase was washed with brine (50 mL), dried over Na2SO4, filtered and the solution concentrated under reduced pressure to give a yellow oil. The crude product was absorbed onto silica gel using dichloromethane and dry-loaded onto a column of silica gel (100 g) packed in hexanes. The column was eluted with hexanes (500 mL), 1% MTME/hexanes (1000 mL) and 2% MTBE/hexanes (1500 mL). Product fractions were concentrated under reduced pressure to give a yellowish-white solid that was pumped under high vacuum overnight to give 3.6 g (75%) of 26.

1. additioncontaining a crystal
2. concentrationThe mixture was concentrated under reduced pressure
3. customto give crude imine 25 as a yellow-brown oil
4. temperaturethe solution cooled to −2° C
5. temperatureto warm to room temperature
6. stirringstirred 1.5 hr
7. temperatureThe mixture was cooled to ˜10° C.
8. customquenched by the slow,
9. additiondropwise addition of saturated NH4Cl solution (20 mL)
10. customthen partitioned between 1:1 EtOAc heptanes (150 mL) and H2O (25 mL)
11. washThe organic phase was washed with brine (50 mL)
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. concentrationthe solution concentrated under reduced pressure
15. customto give a yellow oil
16. customThe crude product was absorbed onto silica gel
17. washThe column was eluted with hexanes (500 mL), 1% MTME/hexanes (1000 mL) and 2% MTBE/hexanes (1500 mL)
18. concentrationProduct fractions were concentrated under reduced pressure
19. customto give a yellowish-white solid
20. customthat was pumped under high vacuum overnight