Sodium hydride → 5,6-Dichloro-1-(3-fluoro-benzyl)-2-(2,2,2-trifluoro-ethyl)-1H-benzoimidazole

HRID 2043281ノート

反応式

HRID 2043281 の反応式
[H-].[Na+].ClC1C2N=C(CC(F)(F)F)[N:9](Cl)C=2C=CC=1.[Cl:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][C:28]=1[Cl:29])[NH:25][C:24]([CH2:30][C:31]([F:34])([F:33])[F:32])=C2.[F:35][C:36]1[CH:37]=[C:38]([CH:41]=[CH:42][CH:43]=1)[CH2:39]Br.[NH4+].[Cl-]>CN(C=O)C>[Cl:29][C:28]1[C:20]([Cl:19])=[CH:21][C:22]2[N:9]([CH2:39][C:38]3[CH:41]=[CH:42][CH:43]=[C:36]([F:35])[CH:37]=3)[C:24]([CH2:30][C:31]([F:32])([F:33])[F:34])=[N:25][C:26]=2[CH:27]=1

参加物

7

反応物 5

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 680073-Fluorobenzyl bromideHCID 669688335,6-Dichloro-2-(2,2,2-trifluoro-ethyl)-1H-indoleHCID 66968977dichloro-2-(2,2,2-trifluoro-ethyl)-1H-benzoimidazole

生成物 1

HCID 444301445,6-Dichloro-1-(3-fluoro-benzyl)-2-(2,2,2-trifluoro-ethyl)-1H-benzoimidazole

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

NaH (60%) (60 mg, 1.5 mmol) was added into a solution of dichloro-2-(2,2,2-trifluoro-ethyl)-1H-benzoimidazole. 5,6-Dichloro-2-(2,2,2-trifluoro-ethyl)-1H-indole (269 mg, 1 mmol) in DMF (5 ml) at 0° C. The resulting mixture was stirred at 0° C. for half hour. 3-fluorobenzyl bromide (283.5 mg, 1.5 mmol) was then added to the reaction mixture at 0° C. The reaction temperature was raised to 25° C. and then the reaction mixture was stirred for 18 hours. NH4Cl (aq.) was added and extracted with EtOAc. The organic layer was washed with brine, then dried over anhydrous MgSO4. The solvent was distilled out under reduced pressure. Column chromatography (silica gel, EtOAc/hexanes (0% to 60%) yielded the title compound as an off-white solid.

後処理

  1. customat 0° C
  2. temperatureThe reaction temperature was raised to 25° C.
  3. stirringthe reaction mixture was stirred for 18 hours
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous MgSO4
  7. distillationThe solvent was distilled out under reduced pressure

出典と根拠

ORDレコード
ord-1df2ab8452aa4ef4be7680e366bbcbb2
出典データセット
uspto-grants-2013_11
特許番号
US08586616B2

反応ノート

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