4-Methylbenzyl chloride → 1-(6-Methylpyridin-2-yl)-2-p-tolyl-ethanone

HRID 8225

反応式

HRID 8225 の反応式
[Mg].[CH3:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7]Cl)=[CH:5][CH:4]=1.CON(C)[C:14]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH3:22])[N:17]=1)=[O:15]>C1(C)C=CC=CC=1.O1CCCC1.BrCCBr>[CH3:22][C:18]1[N:17]=[C:16]([C:14](=[O:15])[CH2:7][C:6]2[CH:9]=[CH:10][C:3]([CH3:2])=[CH:4][CH:5]=2)[CH:21]=[CH:20][CH:19]=1

参加物

7

反応物 3

HCID 77224-Methylbenzyl chloride2 回HCID 5462224MagnesiumHCID 45869585N-methoxy-N,6-dimethylpyridine-2-carboxamide

生成物 1

HCID 219929001-(6-Methylpyridin-2-yl)-2-p-tolyl-ethanone

試薬・触媒・溶媒 3

HCID 78391,2-Dibromoethane触媒HCID 1140Toluene溶媒2 回HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
50 °C

実験手順

To a slurry of magnesium turnings (406 mg, 16.7 mmol) in toluene (10 mL) is added 4-methylbenzylchloride (10 mg, 0.06 mmol) dropwise in tetrahydrofuran (0.2 mL). Two drops of 1,2-dibromoethane are added, the mixture heated to 50° C., and allowed to cool to room temperature. This process is repeated until reaction initiates. 4-Methylbenzylchloride (1.5 g, 10 mmol) in tetrahydrofuran (7 mL) is added slowly while keeping the internal temperature below 32° C. After the addition is complete the reaction is stirred at room temperature for 1 h. The reaction mixture is added dropwise over 5 minutes to a solution of 6-methyl-pyridine-2-carboxylic acid methoxy-methyl-amide (Prep 250, 1 g, 5.6 mmol) in toluene (5 mL). The reaction is stirred for an additional 45 minutes. The reaction is quenched with 1 N hydrochloric acid and stirred for 30 minutes. The aqueous layer is neutralized with saturated sodium bicarbonate and extracted twice with ethyl acetate. The combined organic extracts are washed with brine, dried (sodium sulfate), filtered and concentrated in vacuo. The crude residue is chromatographed on SiO2 (50% ethyl acetate/hexane to 75% ethyl acetate/hexane) to yield the title compound, 633 mg (25%), as a brown oil.

後処理

  1. temperatureto cool to room temperature
  2. customThis process is repeated until reaction initiates
  3. customthe internal temperature below 32° C
  4. additionAfter the addition
  5. stirringThe reaction is stirred for an additional 45 minutes
  6. customThe reaction is quenched with 1 N hydrochloric acid
  7. stirringstirred for 30 minutes
  8. extractionextracted twice with ethyl acetate
  9. washThe combined organic extracts are washed with brine
  10. dry with materialdried (sodium sulfate)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe crude residue is chromatographed on SiO2 (50% ethyl acetate/hexane to 75% ethyl acetate/hexane)

出典と根拠

ORDレコード
ord-4bc2f7f0f41d432a9827529aae96896e
出典データセット
uspto-grants-2006_08
特許番号
US07087626B2

関連ノート

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