反应详情

To a cold (0° C.) solution of sodium hydride (1.80 g, 45.0 mmol) in dimethylformamide (anhydrous,40 mL) and under a nitrogen atmosphere, add dropwise a solution of 3-(6-fluoro-benzo[d]isoxazol-3-yl)-phenol (10 g, 43.63 mmol) in dimethylformamide (anhydrous, 50 mL). Precipitate forms. Cool (0° C.) reaction mixture for 20 minutes and the material solidifies. Add dimethylformamide (anhydrous, 120 mL) and (2R)-(−)-glycidyl tosylate (10.47 g, 45.87 mmol) dissolved in dimethylformamide (40 mL), dropwise, over a period of time of 0.5 hours, while cooling with an ice bath. After this addition, the reaction mixture becomes homogeneous. Warm reaction mixture to room temperature and stir overnight. Pour reaction mixture into cold water (600 mL), stir for 1 hour under an ice bath, filter and wash the filter cake with water to obtain an off-white solid. Add dichloromethane (200 mL) to the off-white solid, wash with saturated sodium chloride and dry (MgSO4). Directly purify by column (silica) chromatography (dichloromethane) and triturate with pentane to give the title compound as an off-white solid (9.70 g, 78% Yield). MS shows [M+H]+=286. NMR and microanalysis (C, H, N) are consistent with the final, desired compound. mp=132-133° C.

1. temperatureCool
2. custom(0° C.) reaction mixture for 20 minutes
3. temperaturewhile cooling with an ice bath
4. additionAfter this addition
5. temperatureWarm
6. customreaction mixture to room temperature
7. additionPour
8. stirringstir for 1 hour under an ice bath
9. filtrationfilter
10. washwash the filter cake with water
11. customto obtain an off-white solid
12. washAdd dichloromethane (200 mL) to the off-white solid, wash with saturated sodium chloride
13. dry with materialdry (MgSO4)
14. customDirectly purify by column (silica) chromatography (dichloromethane)
15. customtriturate with pentane