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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
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HRID 1184091 반응식
[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
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참가 물질

7

반응물 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

생성물 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
수율 28.5%

시약·촉매·용매 2

HCID 962Water용매HCID 6342Acetonitrile용매

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온도
60 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-330ef3e940c54ed69b93b4050c07658d
출처 데이터셋
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08664380B2

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