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Sodium hydride → (3RS)-1-(2-acetylthiophen-3-yl)methyl-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one

HRID 963479
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HRID 963479 반응식
[H-].[Na+].[C:3]([O:7][C:8]([NH:10][CH:11]1[N:17]=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[F:24])[C:15]2[CH:25]=[CH:26][CH:27]=[CH:28][C:14]=2[NH:13][C:12]1=[O:29])=[O:9])([CH3:6])([CH3:5])[CH3:4].[C:30]([C:33]1[S:34][CH:35]=[CH:36][C:37]=1[CH2:38]Br)(=[O:32])[CH3:31]>CN(C)C=O>[C:30]([C:33]1[S:34][CH:35]=[CH:36][C:37]=1[CH2:38][N:13]1[C:14]2[CH:28]=[CH:27][CH:26]=[CH:25][C:15]=2[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[F:24])=[N:17][CH:11]([NH:10][C:8]([O:7][C:3]([CH3:6])([CH3:4])[CH3:5])=[O:9])[C:12]1=[O:29])(=[O:32])[CH3:31]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 19081122(3RS)-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-oneHCID 217012741-[3-(Bromomethyl)thiophen-2-yl]ethan-1-one

생성물 1

HCID 19081290(3RS)-1-(2-acetylthiophen-3-yl)methyl-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one수율 57.9%

시약·촉매·용매 1

HCID 6228
Dimethylformamide
용매
3회

실험 절차

To a suspension of sodium hydride (0.119 g of a 60% dispersion in mineral oil) in dry N,N-dimethylformamide (8 ml) was added dropwise a solution of (3RS)-3-tert-butoxycarbonylamino-2,3-dihydro-5- (2-fluorophenyl)-1H-1,4-benzodiazepin-2-one (1.005 g) in dry N,N-dimethylformamide (5 ml) under stirring at cooling in an ice-bath. The mixture was stirred at the same temperature for 30 minutes and then at room temperature for 1.5 hours. To the mixture was added a solution of 2-acetyl-3-bromomethylthiophen (0.82 g) in N,N-dimethylformamide (3 ml) under cooling in an ice-bath. The mixture was stirred under the same condition for 30 minutes and then at ambient temperature overnignt. The reaction mixture was concentrated in vacuo. The residue was treated with ethyl acetate and water. The organic layer seas washed with water and a brine, and dried over sodium sulfate. Removal of the solvent at reduced pressure gave a crude product. The crude product was purified by column chromatography on silica gel with chloroform as an eluent to give (3RS)-1-(2-acetylthiophen-3-yl)methyl-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one (0.80 g).

후처리

  1. temperatureat cooling in an ice-bath
  2. stirringThe mixture was stirred at the same temperature for 30 minutes
  3. temperatureunder cooling in an ice-bath
  4. stirringThe mixture was stirred under the same condition for 30 minutes
  5. customat ambient temperature
  6. concentrationThe reaction mixture was concentrated in vacuo
  7. additionThe residue was treated with ethyl acetate and water
  8. washThe organic layer seas washed with water
  9. dry with materiala brine, and dried over sodium sulfate
  10. customRemoval of the solvent at reduced pressure
  11. customgave a crude product
  12. customThe crude product was purified by column chromatography on silica gel with chloroform as an eluent

출처 및 근거

ORD 기록
ord-dcf21717d8424a5693bd1aff678fe16d
출처 데이터셋
uspto-grants-1998_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US05763437

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