反应详情

To a cold (0° C.) solution of valerolactam (153.30 g, 1.54 mol) in anhydrous 1-methyl-2-pyrrolidinone (3.5 L), sodium hydride (67.7 g, 1.69 mol, 60% dispersion in oil) was added over a period of 5 minutes. The reaction mixture was stirred for 30 minutes, and a solution of 3-chloro-4-fluorobenzylbromide (345.5 g, 1.54 mol) in 1-methyl-2-pyrrolidinone (200 mL) was added over 30 minutes at 0° C. The reaction mixture was stirred at 0° C. for 1 hour, and was allowed to warm up and stirred at room temperature overnight. The reaction mixture was quenched with distilled water (5 L), and extracted with dichloromethane (three times; 2 L, 1 L, 1 L). The organic extracts were combined, washed with water (3×; 4 L each time). The residual oil was dissolved in ethyl acetate (4 L), and extracted with water (3×; 2 L each time). The organic layer was separated, concentrated under vacuum to give the title product that solidified upon standing.

1. stirringThe reaction mixture was stirred at 0° C. for 1 hour
2. temperatureto warm up
3. stirringstirred at room temperature overnight
4. customThe reaction mixture was quenched with distilled water (5 L)
5. extractionextracted with dichloromethane (three times; 2 L, 1 L, 1 L)
6. washwashed with water (3×; 4 L each time)
7. dissolutionThe residual oil was dissolved in ethyl acetate (4 L)
8. extractionextracted with water (3×; 2 L each time)
9. customThe organic layer was separated
10. concentrationconcentrated under vacuum