4,4-Difluorocyclohexanone → 2-(4,4-Difluorocyclohexylidene)-2-(2-methylpyrimidin-5-yl)acetonitrile

HRID 512178ノート

反応式

HRID 512178 の反応式
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][N:3]=1.[F:11][C:12]1([F:19])[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]1.CC([O-])(C)C.[K+]>O1CCOCC1>[F:11][C:12]1([F:19])[CH2:17][CH2:16][C:15](=[C:8]([C:5]2[CH:4]=[N:3][C:2]([CH3:1])=[N:7][CH:6]=2)[C:9]#[N:10])[CH2:14][CH2:13]1

参加物

5

反応物 3

HCID 157890924,4-DifluorocyclohexanoneHCID 23665647Potassium tert-butoxideHCID 847623642-(2-Methylpyrimidin-5-yl)acetonitrile

生成物 1

HCID 867162052-(4,4-Difluorocyclohexylidene)-2-(2-methylpyrimidin-5-yl)acetonitrile収率 23.5%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
60 °C

実験手順

To a solution of 2-(2-methylpyrimidin-5-yl)acetonitrile (1 g, 7.52 mmol) and 4,4-difluorocyclohexanone (1.1 g, 8.27 mmol) in 1,4-dioxane (40 mL) was added t-BuOK (0.8 g, 8.27 mmol) in two portions. After the addition was completed, the reaction was heated to 60° C. and stirred overnight. The reaction solution was cooled to 0° C., quenched by saturated NH4Cl aq. solution and extracted with EtOAC (50 m×3). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated to get the crude product, which was purified by column chromatography on silica gel (Petroleum ether: EtOAc=4:1˜2:1) to afford 2-(4,4-difluorocyclohexylidene)-2-(2-methylpyrimidin-5-yl)acetonitrile (440 mg, yield: 23.5%). 1H NMR (CDCl3 varian 400 MHz): δ8.61 (s, 2H), 2.97 (t, J=8.0 Hz, 2H), 2.80 (s, 3H), 2.55 (t, J=8.0 Hz, 2H), 2.27-2.17 (m, 2H), 2.09-1.98 (m, 2H).

後処理

  1. additionAfter the addition
  2. temperatureThe reaction solution was cooled to 0° C.
  3. customquenched by saturated NH4Cl aq. solution
  4. extractionextracted with EtOAC (50 m×3)
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customto get the crude product, which
  9. customwas purified by column chromatography on silica gel (Petroleum ether: EtOAc=4:1˜2:1)

出典と根拠

ORDレコード
ord-42bdd4d448c743ecabcc1528721275cc
出典データセット
uspto-grants-2015_08
特許番号
US09102591B2

反応ノート

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