反应详情

To a solution of 5-fluoro-4-(2-hydroxyethyl)-2-methoxybenzonitrile (0.68 g, 3.5 mmol) and Et3N (0.82 mL, 5.9 mmol) in dichloromethane (5 mL) was added methanesulfonyl chloride (0.33 mL, 4.2 mmol) at 0° C. After 15 min. the reaction mixture was poured into saturated ammonium chloride and extracted with dichloromethane. The combined organics were washed with 1 N HCl, saturated sodium bicarbonate solution, and brine, then dried (MgSO4) and concentrated in vacuo. The residue was re-dissolved in dichloromethane (5 mL), treated with DBU (0.79 mL, 5.2 mmol) and stirred for 2 h. TLC monitoring showed conversion to the olefin. The reaction mixture was diluted with water and extracted with dichloromethane. The combined organics were washed with 1 N HCl, saturated sodium bicarbonate solution, and brine, then dried (MgSO4) and concentrated in vacuo. The resulting olefin was dissolved in dichloromethane (5 mL) and treated with meta-chloro perbenzoic acid (0.72 g, 4.2 mmol) at 0° C. After 3 h, the mixture was diluted with saturated sodium bicarbonate solution and extracted with dichloromethane (twice). The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The crude epoxide was purified by silica gel column chromatography (5->80% EtOAc:hexane) to provide 5-fluoro-2-methoxy-4-oxiran-2-ylbenzonitrile. 1H NMR (500 MHz, CD3OD) δ 7.32 (d, J=5.3 Hz, 1H), 6.82 (d, J=5.4 Hz, 1H), 4.19 (m, 1H), 3.96 (s, 3H), 3.27 (m, 1H), 2.76 (m, 1H);

1. extractionextracted with dichloromethane
2. washThe combined organics were washed with 1 N HCl, saturated sodium bicarbonate solution, and brine
3. dry with materialdried (MgSO4)
4. concentrationconcentrated in vacuo
5. dissolutionThe residue was re-dissolved in dichloromethane (5 mL)
6. extractionextracted with dichloromethane
7. washThe combined organics were washed with 1 N HCl, saturated sodium bicarbonate solution, and brine
8. dry with materialdried (MgSO4)
9. concentrationconcentrated in vacuo
10. dissolutionThe resulting olefin was dissolved in dichloromethane (5 mL)
11. waitAfter 3 h
12. extractionextracted with dichloromethane (twice)
13. washThe combined organic extracts were washed with brine
14. dry with materialdried (MgSO4)
15. filtrationfiltered
16. concentrationconcentrated in vacuo
17. customThe crude epoxide was purified by silica gel column chromatography (5->80% EtOAc:hexane)