Methyl chloroformate → 6-Methoxy-2-(4-methoxy-phenyl)-quinoline

HRID 1062582

反応式

HRID 1062582 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N+:9]([O-])=[CH:8][CH:7]=[CH:6]2.COC(Cl)=O.C([Mg]Br)[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)[CH:7]=[CH:6]2

参加物

5

反応物 3

HCID 6586Methyl chloroformateHCID 2538216-Methoxyquinoline N-oxideHCID 178418276HCID 178418276、化合物

生成物 1

HCID 123683166-Methoxy-2-(4-methoxy-phenyl)-quinoline収率 52%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

A 500 mL round-bottom flask is charged with 6-methoxy quinoline-N-oxide (8 g, 0.04566 mol.) and placed under nitrogen. The solid is then dissolved in anhydrous THF (100 mL) and cooled to −78° C. with a dry ice/acetone bath, whereupon some of the dissolved solid begins to precipitate. From an addition funnel, methylchloroformate (4.4 ml, 0.05694 mol.) is added dropwise. The bath is removed 10 minutes after the addition, and replaced after 20 minutes. A dropwise addition of 0.5 M anisylmagnesium bromide (112 mL, 0.0560 mol.) is then made. The bath is removed after the addition and the reaction is allowed to warm to room temperature. The reaction is quenched with 5% sodium bicarbonate solution. The THF is removed in vacuo and the resulting mixture is diluted with water and extracted with methylene chloride. The extracts are collected and dried with anhydrous sodium sulfate and concentrated. The crude product is purified by flash chromatography (2-5% EtOAc/dichloromethane) to yield 6.30 g (52%) of the desired product. 1H NMR: ∂ 8.03-8.11 (m, 4H), 7.78 (d, J=8.8 Hz, 1H), 7.37 (dd, J=9 Hz, 3 Hz, 1H), 7.03-7.07 (m, 3H), 3.94 (s, 1H), 3.88 (s, 1H). LCMS: 2.188 min, 266 (M+).

後処理

  1. customto precipitate
  2. customThe bath is removed 10 minutes
  3. additionafter the addition
  4. customThe bath is removed
  5. additionafter the addition
  6. temperatureto warm to room temperature
  7. customThe reaction is quenched with 5% sodium bicarbonate solution
  8. customThe THF is removed in vacuo
  9. additionthe resulting mixture is diluted with water
  10. extractionextracted with methylene chloride
  11. customThe extracts are collected
  12. dry with materialdried with anhydrous sodium sulfate
  13. concentrationconcentrated
  14. customThe crude product is purified by flash chromatography (2-5% EtOAc/dichloromethane)

出典と根拠

ORDレコード
ord-f92fa587be5649bb82053b12bab0ce92
出典データセット
uspto-grants-2005_11
特許番号
US06962928B2

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