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Sodium hydride → 2-Fluoro-4-(6-hydroxymethyl-4-methyl-2-propyl-benzoimidazol-1-ylmethyl)-benzoic acid methyl ester

HRID 476298
ノート
印刷プレビュー

反応式

HRID 476298 の反応式
[CH3:1][C:2]1[C:7]2[N:8]=[C:9]([CH2:11][CH2:12][CH3:13])[NH:10][C:6]=2[CH:5]=[C:4]([CH2:14][OH:15])[CH:3]=1.[H-].[Na+].[CH3:18][O:19][C:20](=[O:30])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27]Br)=[CH:23][C:22]=1[F:29]>CN(C=O)C>[CH3:18][O:19][C:20](=[O:30])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27][N:10]2[C:6]3[CH:5]=[C:4]([CH2:14][OH:15])[CH:3]=[C:2]([CH3:1])[C:7]=3[N:8]=[C:9]2[CH2:11][CH2:12][CH3:13])=[CH:23][C:22]=1[F:29]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 18759821Methyl 4-(bromomethyl)-2-fluorobenzoateHCID 59868533(7-Methyl-2-propyl-3H-benzoimidazol-5-yl)methanol

生成物 1

HCID 687231872-Fluoro-4-(6-hydroxymethyl-4-methyl-2-propyl-benzoimidazol-1-ylmethyl)-benzoic acid methyl ester収率 43.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
0 °C

実験手順

(7-Methyl-2-propyl-3H-benzoimidazol-5-yl)methanol (3 g, 15 mmol; prepared as described in Preparation 7) was dissolved in 20 mL of dry DMF. The solution was cooled to 0° C. and sodium hydride (598 mg, 15 mmol, 60 wt % in mineral oil) was added. The mixture was stirred for 30 minutes. 4-Bromomethyl-2-fluorobenzoic acid methyl ester (3.7 g, 15 mmol; prepared as described in Preparation 3) in 50 mL of DMF was added, and the mixture was warmed to room temperature and stirred for 10 minutes. The solution was partitioned between EtOAc (300 mL) and 150 mL 10% LiCl (aqueous). The organic layer was separated, dried over MgSO4 and concentrated. The concentrate was flash chromatographed to produce Intermediate (8a) as a clear oil (2.4 g). MS m/z: [M+H+] calcd for C21H23FN2O3, 371.7. found 371.0.

後処理

  1. temperaturethe mixture was warmed to room temperature
  2. stirringstirred for 10 minutes
  3. customThe solution was partitioned between EtOAc (300 mL) and 150 mL 10% LiCl (aqueous)
  4. customThe organic layer was separated
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customchromatographed

出典と根拠

ORDレコード
ord-b3fbf5894c0b4d85b77d038725f794aa
出典データセット
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08637676B2

反応ノート

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