Water → N-benzyl-4-hydroxy-3-oxobutanamide

HRID 526716

반응식

HRID 526716 반응식
[CH2:1]([NH:8][C:9](=[O:14])[CH2:10][C:11](=[O:13])[CH3:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.BrBr.O.C([O-])=[O:19].[K+]>ClCCl>[CH2:1]([NH:8][C:9](=[O:14])[CH2:10][C:11](=[O:13])[CH2:12][OH:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

6

반응물 4

HCID 962Water2회HCID 24408Bromine2회HCID 70159Acetoacetobenzylamide2회HCID 2735122Potassium Formate

생성물 1

HCID 71502813N-benzyl-4-hydroxy-3-oxobutanamide수율 38.8%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
7.5 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-c619e5d24af943a4b31ecc31c061d00b
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346751B2

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