Potassium Carbonate → tert-butyl (3S,5R)-3-[{[6-fluoro-1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

HRID 1184089Notes

Reaction equation

HRID 1184089 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]([CH3:46])[CH2:23][NH:24][C@H:25]1[CH2:30][C@@H:29]([C:31]([N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)=[O:32])[CH2:28][N:27]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:26]1.C(=O)([O-])[O-:48].[K+].[K+]>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]([CH3:46])[CH3:21])[C@H:25]3[CH2:30][C@@H:29]([C:31]([N:33]4[CH2:38][CH2:37][O:36][CH2:35][CH2:34]4)=[O:32])[CH2:28][N:27]([C:39]([O:41][C:42]([CH3:44])([CH3:43])[CH3:45])=[O:40])[CH2:26]3)=[O:48])[N:7]([CH2:14][CH2:15][CH2:16][CH2:17][O:18][CH3:19])[C:6]=2[CH:20]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 583553976-fluoro-1-(4-methoxybutyl)-2-(trichloromethyl)-1H-benzimidazoleHCID 59356577tert-Butyl (3S,5R)-3-(isobutylamino)-5-(morpholine-4-carbonyl)piperidine-1-carboxylate

Product 1

HCID 58355258tert-butyl (3S,5R)-3-[{[6-fluoro-1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylateYield 32.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

6-Fluoro-1-(4-methoxybutyl)-2-(trichloromethyl)-1H-benzimidazole (1.02 g) and tert-butyl (3S,5R)-3-[(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (1.11 g) were dissolved in acetonitrile (50 ml) and water (25 ml), potassium carbonate (4.15 g) was added, and the mixture was stirred at 60° C. for 17 hr. The reaction mixture was cooled to room temperature, and the mixture was extracted with ethyl acetate. The extract was washed successively with 10% aqueous citric acid solution, aqueous sodium bicarbonate and 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 was concentrated under reduced pressure to give the object product (595 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed successively with 10% aqueous citric acid solution, aqueous sodium bicarbonate and 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
  7. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-53a3badc8c654db984b04b4cbcfc9877
Source dataset
uspto-grants-2014_03
Patent number
US08664380B2

Reaction notes

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