Sodium hydride → 5-Formyl-2-{[(1S)-1-methylpropyl]oxy}benzonitrile

HRID 423322

反応式

HRID 423322 の反応式
[CH3:1][C@H:2]([OH:5])[CH2:3][CH3:4].[H-].[Na+].F[C:9]1[CH:16]=[CH:15][C:14]([CH:17]=[O:18])=[CH:13][C:10]=1[C:11]#[N:12]>CN(C=O)C>[CH:17]([C:14]1[CH:15]=[CH:16][C:9]([O:5][C@@H:2]([CH3:1])[CH2:3][CH3:4])=[C:10]([CH:13]=1)[C:11]#[N:12])=[O:18]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 444683(+)-2-ButanolHCID 27695822-Fluoro-5-formylbenzonitrile

生成物 1

HCID 866414335-Formyl-2-{[(1S)-1-methylpropyl]oxy}benzonitrile収率 8.3%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

(2S)-2-Butanol (0.99 g, 0.013 mol) was dissolved in DMF (50 ml) and the solution cooled to 0° C. To this was added sodium hydride, (60% dispersion in mineral oil, 1.54 g, 0.036 mol) in a portion-wise manner, the mixture was stirred at 0° C. for 10 minutes after complete addition. 2-Fluoro-5-formylbenzonitrile (2.0 g, 0.013 mol) was then added and the reaction mixture allowed to warm to room temperature (slowly within the ice bath) and the reaction mixture was stirred overnight at room temperature. The reaction mixture was then cooled to 0° C., quenched with brine and diluted with EtOAc (˜25 ml). The mixture was partitioned and the organic fraction extracted with water (˜30 ml), the combined organics were dried by passing through a phase separating cartridge and then evaporated to dryness under reduced pressure to give the crude product. The crude residue was purified on a 40+M Biotage cartridge, eluting with a 20 to 50% mixture of EtOAc in hexane. This gave the title compound (220 mg) as a white solid. δH (d6-DMSO, 400 MHz): 9.88 (1H, s), 8.30 (1H, s), 8.15 (1H, d), 7.49 (1H, d), 4.73-4.81 (1H, m), 1.63-1.79 (2H, m), 1.33 (3H, d), 0.95 (3H, t). MS (ES): C12H13NO2 requires 203; found 204 (MH+).

後処理

  1. additionafter complete addition
  2. stirringwas stirred overnight at room temperature
  3. temperatureThe reaction mixture was then cooled to 0° C.
  4. customquenched with brine
  5. additiondiluted with EtOAc (˜25 ml)
  6. customThe mixture was partitioned
  7. extractionthe organic fraction extracted with water (˜30 ml)
  8. customthe combined organics were dried
  9. customseparating cartridge
  10. customevaporated to dryness under reduced pressure
  11. customto give the crude product
  12. customThe crude residue was purified on a 40+M Biotage cartridge
  13. washeluting with a 20 to 50% mixture of EtOAc in hexane

出典と根拠

ORDレコード
ord-2f6ac0bf2dbd46f696b99d84fdc13460
出典データセット
uspto-grants-2012_01
特許番号
US08101775B2

関連ノート

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