反应详情

A slurry of 5% palladium on charcoal (20 g) in ethanol (100 ml) was added under nitrogen gas to a solution of the above 2-bromo3-chloro-5-(4-fluorobenzoyl)-thiophene (299.4 9 ) in ethanol (3.400 ml), containing sodium acetate (77.0 g),and the mixture was hydrogenated for 3 hours at room temperature and pressure (total uptake of hydrogen was 22,994 ml). The reaction mixture was filtered through a dicalite pad and the pad was washed with ethanol (2×200 ml). The filtrate was taken to low volume (approximately 2 l) and added to water (17 l). The precipitate was filtered and while damp it was dissolved in dichloromethane (1 l) which was then reduced in volume to approximately 500 ml. Methanol (500 ml) was added and the remainder of the dichloromethane was removed by distillation. The resultant crystals were filtered and dried to give 4-chloro-2-(4-fluorobenzoyl)thiophene as a white solid (169 g). A second crop (19.2 g) was obtained and recrystallised from dichloromethane/methanol to give more of the purified product (12.9 g). The crops were combined and used in the next stage.

1. filtrationThe reaction mixture was filtered through a dicalite pad
2. washthe pad was washed with ethanol (2×200 ml)
3. additionadded to water (17 l)
4. filtrationThe precipitate was filtered and while damp it
5. dissolutionwas dissolved in dichloromethane (1 l) which
6. additionMethanol (500 ml) was added
7. customthe remainder of the dichloromethane was removed by distillation
8. filtrationThe resultant crystals were filtered
9. customdried