Water → 2-Difluoromethoxy-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-benzonitrile

HRID 1172692ノート

反応式

HRID 1172692 の反応式
[CH3:1][C:2]1[N:3]=[C:4]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[S:5][C:6]=1[CH:7]([OH:10])[CH2:8][CH3:9].[H-].[Na+].[F:23][CH:24]([F:35])[O:25][C:26]1[CH:33]=[C:32](F)[CH:31]=[CH:30][C:27]=1[C:28]#[N:29].O>CN(C)C=O>[F:23][CH:24]([F:35])[O:25][C:26]1[CH:33]=[C:32]([O:10][CH:7]([C:6]2[S:5][C:4]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:18])[F:19])=[CH:13][CH:12]=3)=[N:3][C:2]=2[CH3:1])[CH2:8][CH3:9])[CH:31]=[CH:30][C:27]=1[C:28]#[N:29]

参加物

6

反応物 4

HCID 962WaterHCID 24758Sodium hydrideHCID 235491291-[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propan-1-olHCID 59295388HCID 59295388、化合物

生成物 1

HCID 595563432-Difluoromethoxy-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-benzonitrile収率 43.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒3 回

反応条件

温度
5 °C

実験手順

To a solution of 1.7 g of 1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propan-1-ol in 4.7 mL of dimethylformamide at 5° C. was added 250 mg of a 55% suspension of sodium hydride in mineral oil. The reaction volume was completed with dimethylformamide to about 8.5 mL. The reaction mixture was stirred for 30 minutes at 5° C. 4.3 mL of the resulting mixture was slowly added to a solution of 450 mg of 2-difluoromethoxy-4-fluoro-benzonitrile in 2 mL of dimethylformamide at 5° C. The resulting mixture was stirred at 5° C. allowing the temperature to warm up to room temperature. It was then heated in a sealed tube to 60° C. under microwave irradiation for 15 minutes. After allowing it to cool down to room temperature, the mixture was poured into water and extracted with dichloromethane. The organic extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (gradient from heptane 100 to heptane 50/ethyl acetate 50) to give 490 mg of 2-difluoromethoxy-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-benzonitrile.

後処理

  1. stirringThe resulting mixture was stirred at 5° C.
  2. temperatureto warm up to room temperature
  3. temperatureIt was then heated in a sealed tube to 60° C. under microwave irradiation for 15 minutes
  4. temperatureto cool down to room temperature
  5. extractionextracted with dichloromethane
  6. dry with materialThe organic extracts were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by column chromatography on silica gel (gradient from heptane 100 to heptane 50/ethyl acetate 50)

出典と根拠

ORDレコード
ord-5aec2aa838204ffcae4d358ec8e1b94b
出典データセット
uspto-grants-2010_11
特許番号
US07834030B2

反応ノート

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