反应详情

A solution of 2-fluoro-4-nitrobenzotrifluoride (12.4 g, 59.3 mmol, 1.0 eq) and (R)-1-methyl-pyrrolidin-3-ol (6.0 g, 59.3 mmol, 1.0 eq) in anhydrous tetrahydrofuran (150 ml) was cooled to 0° C. then slowly treated with portions of 60% sodium hydride (4.7 g, 0.12 mol, 2 eq) over 5 min. Without removing the ice bath, the reaction was allowed to come to room temperature and stir for 48 hrs. Quenched with water (50 ml) and brine (100 ml) then extracted into diethyl ether (5×100 ml). Extracts dried over anhydrous magnesium sulfate and decolorizing charcoal for 1 hr. Filtered through Celite. The filtrate was treated with silica (35 g) then evaporated to give the crude product suspended on silica. Column chromatography on silica (1% MeOH/EtOAc→5% MeOH/EtOAc) gave the product (Rf≡0.3 in 1% MeOH/EtOAc) as an orange oil (7.85 g, 46%).

1. customWithout removing the ice bath
2. customto come to room temperature
3. customQuenched with water (50 ml) and brine (100 ml)
4. extractionthen extracted into diethyl ether (5×100 ml)
5. dry with materialExtracts dried over anhydrous magnesium sulfate
6. customfor 1 hr
7. filtrationFiltered through Celite
8. additionThe filtrate was treated with silica (35 g)
9. customthen evaporated
10. customto give the crude product