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Hydrochloric Acid → 1-tert-Butyl 3-methyl(3R,5S)-5-[{[6-fluoro-1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-1,3-dicarboxylate

HRID 1184091
ノート
印刷プレビュー

反応式

HRID 1184091 の反応式
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C:10](Cl)(Cl)Cl)[N:7]([CH2:14][CH2:15][CH2:16][CH2:17][O:18][CH3:19])[C:6]=2[CH:20]=1.[CH3:21][CH:22]([CH3:42])[CH2:23][NH:24][C@@H:25]1[CH2:30][N:29]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:28][C@H:27]([C:38]([O:40][CH3:41])=[O:39])[CH2:26]1.C(=O)([O-])[O-:44].[Cs+].[Cs+].Cl>C(#N)C.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C:10]([N:24]([CH2:23][CH:22]([CH3:42])[CH3:21])[C@@H:25]3[CH2:30][N:29]([C:31]([O:33][C:34]([CH3:36])([CH3:37])[CH3:35])=[O:32])[CH2:28][C@H:27]([C:38]([O:40][CH3:41])=[O:39])[CH2:26]3)=[O:44])[N:7]([CH2:14][CH2:15][CH2:16][CH2:17][O:18][CH3:19])[C:6]=2[CH:20]=1
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

7

反応物 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 583553976-fluoro-1-(4-methoxybutyl)-2-(trichloromethyl)-1H-benzimidazoleHCID 593566071-tert-butyl 3-methyl (3R,5S)-5-[(2-methylpropyl)amino]piperidine-1,3-dicarboxylate

生成物 1

HCID 583556301-tert-Butyl 3-methyl(3R,5S)-5-[{[6-fluoro-1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-1,3-dicarboxylate
収率 28.5%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
60 °C

実験手順

6-Fluoro-1-(4-methoxybutyl)-2-(trichloromethyl)-1H-benzimidazole (3.40 g) and 1-tert-butyl 3-methyl (3R,5S)-5-[(2-methylpropyl)amino]piperidine-1,3-dicarboxylate (3.14 g) were dissolved in acetonitrile (100 ml) and water (50 ml), cesium carbonate (32.6 g) was added, and the mixture was stirred at 60° C. for 17 hr. The reaction mixture was cooled to room temperature, adjusted to pH 7 with 1M hydrochloric acid, and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:1) was concentrated under reduced pressure to give 1-tert-butyl 3-methyl (3R,5S)-5-[{[6-fluoro-1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-1,3-dicarboxylate (1.60 g), and a fraction eluted with ethyl acetate was concentrated under reduced pressure to give (3R,5S)-1-(tert-butoxycarbonyl)-5-[{[6-fluoro-1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-3-carboxylic acid (1.36 g).

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. washa fraction eluted with ethyl acetate-hexane (1:1)
  7. concentrationwas concentrated under reduced pressure

出典と根拠

ORDレコード
ord-330ef3e940c54ed69b93b4050c07658d
出典データセット
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08664380B2

反応ノート

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