反应详情

A mixture of 21 (1.88 g, 7 mmol, 1.0 equiv), o-anisidine (0.86 g, 0.79 mL, 7 mmol, 1.0 equiv), toluene (35 mL) and a crystal of p-toluenesulfonic acid was refluxed for 4 hr with H2O removal (Dean-Stark trap). The mixture was cooled to room temperature and concentrated under reduced pressure to give crude imine 22 as a yellow-brown oil. Crude 22 was dissolved in THF (25 mL) and the solution cooled to ˜2° C. 3M MeMgBr in THF (5 mL, 15 mmol, 2.15 equiv) was added dropwise via syringe. A green color developed followed by a yellow-brown color. The reaction mixture was allowed to warm to room temperature and stirred overnight. The mixture was cooled to ˜10° C., quenched by the slow, dropwise addition of saturated NH4Cl solution (10 mL) then partitioned between EtOAc (100 mL) and H2O (20 mL). The organic phase was washed with brine (2×40 mL), dried over Na2SO4, filtered and the solution concentrated under reduced pressure to give a brown oil. The crude product was absorbed onto silica gel using dichloromethane and dry-loaded onto a column of silica gel (30 g) packed in heptanes. The column was eluted with heptanes (100 mL), 2% EtOAc/heptanes (200 mL) and 3% EtOAc/heptanes (200 mL). Product fractions were concentrated under reduced pressure to give 2.3 g (85%) 23 as a yellow oil.

1. concentrationconcentrated under reduced pressure
2. customto give crude imine 22 as a yellow-brown oil
3. temperaturethe solution cooled to ˜2° C
4. temperatureto warm to room temperature
5. temperatureThe mixture was cooled to ˜10° C.
6. customquenched by the slow,
7. additiondropwise addition of saturated NH4Cl solution (10 mL)
8. customthen partitioned between EtOAc (100 mL) and H2O (20 mL)
9. washThe organic phase was washed with brine (2×40 mL)
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationthe solution concentrated under reduced pressure
13. customto give a brown oil
14. customThe crude product was absorbed onto silica gel
15. washThe column was eluted with heptanes (100 mL), 2% EtOAc/heptanes (200 mL) and 3% EtOAc/heptanes (200 mL)
16. concentrationProduct fractions were concentrated under reduced pressure