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

HRID 450872ノート

反応式

HRID 450872 の反応式
[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]

参加物

7

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-溶媒

反応条件

温度
-60 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-d120c5c9d72f4d19817c05b03cfe634a
出典データセット
uspto-grants-2013_07
特許番号
US08487000B2

反応ノート

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