Hydrochloric Acid → HCID 58355630, compound

HRID 1259914Notes

Reaction equation

HRID 1259914 reaction equation
[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

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 583553976-fluoro-1-(4-methoxybutyl)-2-(trichloromethyl)-1H-benzimidazoleHCID 59356607HCID 59356607, compound

Product 1

HCID 58355630HCID 58355630, compoundYield 28.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-9dd0f956ee564f4e869459875cb8c53d
Source dataset
uspto-grants-2013_06
Patent number
US08466282B2

Reaction notes

Loading…