Pyrazole → 1-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-1H-pyrazole-3-carboxylic acid methyl ester

HRID 1505284ノート

反応式

HRID 1505284 の反応式
[CH3:1][O:2][C:3]([C:5]1[CH:9]=[CH:8][NH:7][N:6]=1)=[O:4].[H-].[Na+].Cl[C:13]1[CH2:17][C:16]([C:22]2[CH:27]=[C:26]([Cl:28])[CH:25]=[C:24]([Cl:29])[CH:23]=2)([C:18]([F:21])([F:20])[F:19])[O:15][N:14]=1.N1C=CC=N1>C(#N)C>[CH3:1][O:2][C:3]([C:5]1[CH:9]=[CH:8][N:7]([C:13]2[CH2:17][C:16]([C:22]3[CH:27]=[C:26]([Cl:28])[CH:25]=[C:24]([Cl:29])[CH:23]=3)([C:18]([F:19])([F:20])[F:21])[O:15][N:14]=2)[N:6]=1)=[O:4]

参加物

6

反応物 4

HCID 1048PyrazoleHCID 24758Sodium hydrideHCID 584979653-Chloro-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazoleHCID 178498454HCID 178498454、化合物

生成物 1

HCID 584979901-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-1H-pyrazole-3-carboxylic acid methyl ester収率 84.2%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒2 回

実験手順

To a solution of pyrazole-3-carboxylic acid methyl ester (504 mg) in acetonitrile (25 ml) under argon was added sodium hydride (160 mg). The reaction mixture was stirred at room temperature for 1 h. 15 mf of this solution was added dropwise to a solution of chloroisoxazoline of example 17.2 (630 mg) in acetonitrile (10 ml). It was then stirred at room temperature for 1 h; 10 ml of pyrazole solution was added again and the mixture was stirred for 1.5 hour. The reaction was quenched by adding water and dichloromethane. The two layers were separated. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The crude residue was purified by column chromatography (from c-Hex (100%) to c-Hex:EtOAc (80:20)) to afford the title intermediate (680 mg). 1H-NMR (CDCl3, 400 MHz): 8.15 (s, 1H), 7.5 (m, 2H), 7.45 (m, 1H), 4.45 (d, 1H), 4.10 (d, 1H), 3.95 (s, 3H).

後処理

  1. stirringIt was then stirred at room temperature for 1 h
  2. stirringthe mixture was stirred for 1.5 hour
  3. customThe reaction was quenched
  4. additionby adding water and dichloromethane
  5. customThe two layers were separated
  6. extractionThe aqueous layer was extracted with dichloromethane
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customThe crude residue was purified by column chromatography (from c-Hex (100%) to c-Hex:EtOAc (80:20))

出典と根拠

ORDレコード
ord-82bd5e286454424e9042eabc1fe637b3
出典データセット
uspto-grants-2015_12
特許番号
US09216973B2

反応ノート

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