Acetic Acid → 4-(2,6-Difluorophenyl)-2,2-dimethyl-5-oxopiperazine-1-carboxylic acid t-butyl ester

HRID 1694927노트

반응식

HRID 1694927 반응식
CC(C)([O-])C.[K+].[C:7]([O:11][C:12](=[O:31])[NH:13][C:14]([CH3:30])([CH3:29])[CH2:15][N:16]([C:25](=[O:28])[CH2:26]Br)[C:17]1[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=1[F:24])([CH3:10])([CH3:9])[CH3:8].C(O)(=O)C>O1CCCC1>[C:7]([O:11][C:12]([N:13]1[CH2:26][C:25](=[O:28])[N:16]([C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])[CH2:15][C:14]1([CH3:30])[CH3:29])=[O:31])([CH3:10])([CH3:9])[CH3:8]

참가 물질

5

반응물 3

HCID 176Acetic AcidHCID 23665647Potassium tert-butoxideHCID 66645630{2-[(2-Bromoacetyl)-(2,6-difluorophenyl)amino]-1,1-dimethylethyl}carbamic acid t-butyl ester

생성물 1

HCID 666456784-(2,6-Difluorophenyl)-2,2-dimethyl-5-oxopiperazine-1-carboxylic acid t-butyl ester수율 83%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A solution of 2.05 g of potassium t-butoxide (18.3 mmol) in tetrahydrofuran (120 ml) was added to a solution of 5.14 g of {2-[(2-bromoacetyl)-(2,6-difluorophenyl)amino]-1,1-dimethylethyl}carbamic acid t-butyl ester obtained in Example (60b) (12.2 mmol) in tetrahydrofuran (120 ml) under a nitrogen atmosphere and under cooling in a dry ice-acetone bath over 30 minutes, and the mixture was stirred at the same temperature for 30 minutes. 0.33 ml of acetic acid (6.10 mmol) was added to the reaction mixture. After returning to room temperature, the solvent was evaporated under reduced pressure. The residue was diluted with water, followed by extraction with ethyl acetate. Then, the organic layer was washed with brine and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:hexane/ethyl acetate=3/1) to obtain 3.43 g of the title compound (yield: 83%).

후처리

  1. temperatureunder cooling in a dry ice-acetone bath over 30 minutes
  2. customAfter returning to room temperature
  3. customthe solvent was evaporated under reduced pressure
  4. additionThe residue was diluted with water
  5. extractionfollowed by extraction with ethyl acetate
  6. washThen, the organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationAfter filtration
  9. customthe solvent was evaporated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (elution solvent:hexane/ethyl acetate=3/1)

출처 및 근거

ORD 기록
ord-31a4beba274545a290523db3e813ff96
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08158790B2

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