Sodium hydride → HCID 68266063, compound

60% Sodium hydride in oil dispersion (1.2 g, 29.88 mmol) was added portionwise over 5 mins to an ice-cooled, stirred solution of N-(3-bromo-4-fluoro-phenyl)-4-chloro-butanamide (which may be prepared as described in Description 57) (8 g, 27.16 mmol) in dry THF (150 mL) under N2. After cooling for a further 5 mins the cooling bath was removed and the mixture stirred at ambient temp for 2 hours. The reaction mixture was then treated with AcOH (1 ml) by dropwise addition. The mixture was evaporated and the residue partitioned between DCM (150 ml) and water (150 ml). The latter was re-extracted with DCM (50 ml) and the combined organic extracts dried (MgSO4) and evaporated to a white solid. The solid was dissolved in refluxing Et2O (65 ml) and the solution diluted with iso-hexane (240 ml) and left to stand for 1 hour. The crystalline solid was filtered and dried. The filtrate was concentrated to approx 50 ml volume and a 2nd crop of crystals was collected and dried. The combined mass gave N-(3-bromo-4-fluoro-phenyl)pyrrolidin-2-one (D58) (6.03 g);

1. temperaturecooled
2. temperatureAfter cooling for a further 5 mins the cooling bath
3. customwas removed
4. additionThe reaction mixture was then treated with AcOH (1 ml) by dropwise addition
5. customThe mixture was evaporated
6. customthe residue partitioned between DCM (150 ml) and water (150 ml)
7. extractionThe latter was re-extracted with DCM (50 ml)
8. dry with materialthe combined organic extracts dried (MgSO4)
9. customevaporated to a white solid
10. dissolutionThe solid was dissolved
11. temperaturein refluxing Et2O (65 ml)
12. additionthe solution diluted with iso-hexane (240 ml)
13. waitleft
14. waitto stand for 1 hour
15. filtrationThe crystalline solid was filtered
16. customdried
17. concentrationThe filtrate was concentrated to approx 50 ml volume
18. customa 2nd crop of crystals was collected
19. customdried

ORD record

ord-4f0431b4067d4b23be56c7df25be6ef7

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09376436B2