tert-Butyl bromoacetate → tert-Butyl 4-(2,6-difluorophenyl)-4-oxobutyrate

HRID 251542

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HRID 251542 반응식
[CH3:1][C:2]([C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[F:11])=[O:3].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]>C1COCC1.CN1C(=O)N(C)CCC1.CCOC(C)=O>[F:11][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([F:10])[C:4]=1[C:2](=[O:3])[CH2:1][CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]

참가 물질

7

반응물 3

HCID 79177tert-Butyl bromoacetateHCID 836431-(2,6-Difluorophenyl)ethan-1-oneHCID 2733832Lithium Hexamethyldisilazide

생성물 1

HCID 21964547tert-Butyl 4-(2,6-difluorophenyl)-4-oxobutyrate

시약·촉매·용매 3

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-용매

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온도
-60 °C

실험 절차

To a stirred solution of 2,6-Difluoroacetophenone (5 g, 32 mmol) in dry THF (40 ml) and DMPU (8 ml) was added a solution of lithium bis(trimethylsilyl)amide (1.0M, 45 ml) at −60° C. under argon. After stirring for 10 minutes at −60° C., tert-Butyl bromoacetate (6.99 g, 35.8 mmol) was added rapidly. The reaction mixture was stirred for an additional 10 minutes and then warmed to room temperature for 4 hours. The crude mixture was taken in EtOAc and washed with water and brine. The aqueous layer was extracted one more time with EtOAc. The combined organic layers were dried over Na2SO4, filtered, concentrated and purified by flash chromatography on a silica gel column (hex:ethyl acetate, 2:1) to provide the title compound.

후처리

  1. stirringThe reaction mixture was stirred for an additional 10 minutes
  2. temperaturewarmed to room temperature for 4 hours
  3. washwashed with water and brine
  4. extractionThe aqueous layer was extracted one more time with EtOAc
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by flash chromatography on a silica gel column (hex:ethyl acetate, 2:1)

출처 및 근거

ORD 기록
ord-f308335789224b0fb28c4cffb0de095b
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07863475B2

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