5-bromo-1-(4-fluorophenyl)-1H-indazole → 1-allyl-4-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-1H-pyrrole-2-carboxylic acid ethyl ester

HRID 244436ノート

反応式

HRID 244436 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[N:6]=[CH:5]2.[Li]CCCC.[CH2:23]([O:25][C:26]([C:28]1[N:29]([CH2:39][CH:40]=[CH2:41])[CH:30]=[C:31]([C:33](=[O:38])[C:34]([F:37])([F:36])[F:35])[CH:32]=1)=[O:27])[CH3:24]>C1COCC1>[CH2:23]([O:25][C:26]([C:28]1[N:29]([CH2:39][CH:40]=[CH2:41])[CH:30]=[C:31]([C:33]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[N:7]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[N:6]=[CH:5]3)([OH:38])[C:34]([F:36])([F:35])[F:37])[CH:32]=1)=[O:27])[CH3:24]

参加物

5

反応物 3

HCID 468307945-bromo-1-(4-fluorophenyl)-1H-indazoleHCID 594372701-allyl-4-(2,2,2-trifluoroacetyl)-1H-pyrrole-2-carboxylic acid ethyl esterHCID 178418339Butyllithium

生成物 1

HCID 249590981-allyl-4-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-1H-pyrrole-2-carboxylic acid ethyl ester収率 32%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a chilled (−78° C.) solution of 5-bromo-1-(4-fluorophenyl)-1H-indazole (2.0 g, 6.8 mmol, 1.2 equiv.) in 20 mL of THF was added n-BuLi (2.5 mL, 6.2 mmol, 1.1 equiv.) followed by a chilled (−78° C.) solution of 1-allyl-4-(2,2,2-trifluoroacetyl)-1H-pyrrole-2-carboxylic acid ethyl ester (1.6 g, 5.7 mmol, 1.0 equiv.) in 3 mL of THF in one portion. After 30 minutes, the mixture was quenched with water, warmed to room temperature, diluted with brine, and extracted with EtOAc. The combined organics were dried, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (5-30% EtOAc-hexanes) to provide 890 mg (32%) of the title compound as a pale orange solid. MS m/z 488.30 (MH+).

後処理

  1. customthe mixture was quenched with water
  2. additiondiluted with brine
  3. extractionextracted with EtOAc
  4. customThe combined organics were dried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (5-30% EtOAc-hexanes)

出典と根拠

ORDレコード
ord-d1584bbe2e8e471aab5d2d64c44a349a
出典データセット
uspto-grants-2014_02
特許番号
US08658637B2

反応ノート

読み込み中…