(3-Chloro-2-fluorophenyl)hydrazine → 4-(6-chloro-3-ethyl-7-fluoro-1H-indol-2-yl)-2-hydroxy-benzoic acid methyl ester

HRID 1160795ノート

反応式

HRID 1160795 の反応式
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7]([C:10](=O)[CH2:11][CH2:12][CH3:13])=[CH:6][C:5]=1[OH:15].[Cl:17][C:18]1[C:19]([F:26])=[C:20]([NH:24]N)[CH:21]=[CH:22][CH:23]=1>C(O)(=O)C.[Cl-].[Zn+2].[Cl-]>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[NH:24][C:20]3[C:21]([C:11]=2[CH2:12][CH3:13])=[CH:22][CH:23]=[C:18]([Cl:17])[C:19]=3[F:26])=[CH:6][C:5]=1[OH:15]

参加物

5

反応物 2

HCID 2778381(3-Chloro-2-fluorophenyl)hydrazineHCID 595180214-Butyryl-2-hydroxy-benzoic acid methyl ester

生成物 1

HCID 595180204-(6-chloro-3-ethyl-7-fluoro-1H-indol-2-yl)-2-hydroxy-benzoic acid methyl ester

試薬・触媒・溶媒 2

HCID 3007855Zincchloride触媒HCID 176Acetic Acid溶媒

反応条件

温度
120 °C

実験手順

A mixture of 4-butyryl-2-hydroxy-benzoic acid methyl ester (60 mg, 0.27 mmol), (3-chloro-2-fluoro-phenyl)-hydrazine (Apollo Scientific, Ltd., 54 mg, 0.27 mmol), and zinc chloride (110 mg, 0.8 mmol) in acetic acid (2 mL) is purged with nitrogen for 5 minutes and then heated in a sealed tube at 120° C. for 2 hours. The mixture is cooled to room temperature and diluted with ethyl acetate. The resulting mixture is sequentially washed with saturated aqueous Na2CO3 and saturated aqueous NaCl, and finally dried over sodium sulfate. After concentration, the crude product is purified via silica gel flash column chromatography (10% ethyl acetate in hexanes) to afford 4-(6-chloro-3-ethyl-7-fluoro-1H-indol-2-yl)-2-hydroxy-benzoic acid methyl ester as a light yellow solid: ESMS m/z 348.1 (M+H+).

後処理

  1. customis purged with nitrogen for 5 minutes
  2. temperatureThe mixture is cooled to room temperature
  3. additiondiluted with ethyl acetate
  4. washThe resulting mixture is sequentially washed with saturated aqueous Na2CO3 and saturated aqueous NaCl
  5. dry with materialfinally dried over sodium sulfate
  6. concentrationAfter concentration
  7. customthe crude product is purified via silica gel flash column chromatography (10% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-c96e38f34770433eaef37cda5194a561
出典データセット
uspto-grants-2010_10
特許番号
US07816542B2

反応ノート

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