反应详情

温度

7.5 °C

To a solution of N-benzyl-3-oxobutanamide (compound A 50 g, 261 mmol) in dichloromethane (350 ml) was added bromine (14.82 ml, 288 mmol) at 0-5° C., then stirred at 20-25° C. for 3 hours (bromine colour disappeared). Water (300 ml) was added to the mixture with stirring, stirred for 10 min. Organic phase was separated, washed with sodium bicarbonate solution, dried, evaporated to dryness (compound B). The solid residue (compound B) dissolved in methanol (900 ml), added potassium formate (44.0 g, 523 mmol) and the mixture was heated under reflux for 2 hours. Methanol was removed on a rotavap, the residue was taken up into ethyl acetate (EA) (500 ml) under reflux, filtered hot, the filter cake washed with warm EA (100 ml). The combined filtrate was cooled to 5-10° C., aged for 1.5 hours. The precipitate was collected, washed with cold EA (50 ml), dried to give 25 g (46.1%) of crude product, light beige. Re-crystallised from water (300 ml), with active carbon (1 g). Filtered hot on celite, cooled in ice, aged for 1 hour, crystals collected, washed with cold water (20 ml), dried on air overnight to give N-benzyl-4-hydroxy-3-oxobutanamide (21 g, 101 mmol, 38.8% yield).

1. stirringstirred for 10 min
2. customOrganic phase was separated
3. washwashed with sodium bicarbonate solution
4. customdried
5. customevaporated to dryness (compound B)
6. dissolutionThe solid residue (compound B) dissolved in methanol (900 ml)
7. temperaturethe mixture was heated
8. temperatureunder reflux for 2 hours
9. customMethanol was removed on a rotavap
10. temperatureunder reflux
11. filtrationfiltered hot
12. washthe filter cake washed with warm EA (100 ml)
13. customThe precipitate was collected
14. washwashed with cold EA (50 ml)
15. customdried
16. customto give 25 g (46.1%) of crude product
17. filtrationFiltered hot on celite
18. temperaturecooled in ice
19. waitaged for 1 hour
20. customcrystals collected
21. washwashed with cold water (20 ml)
22. customdried on air overnight