Potassium Carbonate → HCID 67321380, compound

HRID 1184069Notes

Reaction equation

HRID 1184069 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[C:11]2[C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[C:20](Cl)(Cl)[Cl:21].[CH3:24][CH:25]([CH3:49])[CH2:26][NH:27][C@H:28]1[CH2:33][C@@H:32]([C:34]([N:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)=[O:35])[CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29]1.C(=O)([O-])[O-:51].[K+].[K+]>C(#N)C.O>[ClH:21].[ClH:21].[CH3:24][CH:25]([CH3:49])[CH2:26][N:27]([C@H:28]1[CH2:33][C@@H:32]([C:34]([N:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)=[O:35])[CH2:31][NH:30][CH2:29]1)[C:20]([CH:8]1[N:7]([CH2:6][CH2:5][CH2:4][CH2:3][O:2][CH3:1])[C:11]2[C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=[CH:15][C:10]=2[NH:9]1)=[O:51]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 58355463HCID 58355463, compoundHCID 59356577tert-Butyl (3S,5R)-3-(isobutylamino)-5-(morpholine-4-carbonyl)piperidine-1-carboxylate

Product 1

HCID 67321380HCID 67321380, compoundYield 2.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

Methyl 1-(4-methoxybutyl)-2-(trichloromethyl)-1H-benzimidazole-7-carboxylate (0.44 g) and tert-butyl (3S,5R)-3-[(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (0.3 g) were dissolved in acetonitrile (5.0 ml) and water (5.0 ml), potassium carbonate (2.4 g) was added, and the mixture was stirred at 60° C. overnight. 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 magnesium 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 (0:10→10:0) was concentrated under reduced pressure, and a fraction eluted with ethyl acetate was concentrated under reduced pressure. The residue was dissolved in 4N hydrochloric acid-ethyl acetate solution, and the mixture was stirred for 30 min. The reaction mixture was concentrated, purified by HPLC, and the object fraction was concentrated, diluted with aqueous calcium carbonate solution and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and converted to hydrochloride with 4N hydrochloric acid-ethyl acetate solution to give the object product (9.3 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 magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. washa fraction eluted with ethyl acetate-hexane (0:10→10:0)
  7. concentrationwas concentrated under reduced pressure
  8. washa fraction eluted with ethyl acetate
  9. concentrationwas concentrated under reduced pressure
  10. dissolutionThe residue was dissolved in 4N hydrochloric acid-ethyl acetate solution
  11. stirringthe mixture was stirred for 30 min
  12. concentrationThe reaction mixture was concentrated
  13. custompurified by HPLC
  14. concentrationthe object fraction was concentrated
  15. additiondiluted with aqueous calcium carbonate solution
  16. extractionthe mixture was extracted with ethyl acetate
  17. washThe extract was washed with saturated brine
  18. dry with materialdried over anhydrous magnesium sulfate
  19. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-6741e323e1524f6e941c7e69622bebff
Source dataset
uspto-grants-2014_03
Patent number
US08664380B2

Reaction notes

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