反应详情

温度

0 °C

Valerolactam (153.3 g, 1.54 mol) was dissolved in NMP (3.5 L) and cooled to 0° C. NaH (67.7 g, 1.69 mol, 60% dispersion in oil) was added in portions over 5 minutes keeping the temperature at 0° C. The reaction was stirred for 30 minutes, and 3-chloro-4-fluorobenzylbromide (345.5 g, 1.54 mol) dissolved in 200 mL NMP was added over 30 minutes, again keeping the internal temperature at 0° C. The reaction was aged for 1 hour at 0° C., and allowed to warm to room temperature overnight. LCMS showed the reaction complete. The reaction mixture was quenched with 5 L distilled H2O, extracted with 3 portions of CH2Cl2 (2 L, 1 L, 1 L) and the organic layers combined and washed with three 4 L portions of water. The organic layer was concentrated and was found to contain NMP. The residual oil was dissolved in EtOAc (4 L), and extracted with three 2 L portions of water. The organic layer was concentrated to give the product that solidified upon standing.

1. customat 0° C
2. additionwas added over 30 minutes
3. customat 0° C
4. waitThe reaction was aged for 1 hour at 0° C.
5. temperatureto warm to room temperature overnight
6. customThe reaction mixture was quenched with 5 L
7. distillationdistilled H2O
8. extractionextracted with 3 portions of CH2Cl2 (2 L, 1 L, 1 L)
9. washwashed with three 4 L portions of water
10. concentrationThe organic layer was concentrated
11. dissolutionThe residual oil was dissolved in EtOAc (4 L)
12. extractionextracted with three 2 L portions of water
13. concentrationThe organic layer was concentrated
14. customto give the product that