Hydrochloric Acid → HCID 58355539, compound

HRID 1184192Notes

Reaction equation

HRID 1184192 reaction equation
C([O:3][C:4](=O)[CH2:5][CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[C:16]([N:18]([CH2:40][CH:41]([CH3:43])[CH3:42])[C@H:19]1[CH2:24][C@@H:23]([C:25]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[O:26])[CH2:22][N:21]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:20]1)=[O:17])C.[OH-].[Na+].Cl>C(O)C>[CH3:16][C:8]1[N:9]=[C:4]([CH2:5][CH2:6][N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C:16]([N:18]([CH2:40][CH:41]([CH3:43])[CH3:42])[C@H:19]2[CH2:24][C@@H:23]([C:25]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)=[O:26])[CH2:22][N:21]([C:33]([O:35][C:36]([CH3:37])([CH3:38])[CH3:39])=[O:34])[CH2:20]2)=[O:17])[O:3][N:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 58355516HCID 58355516, compound

Product 1

HCID 58355539HCID 58355539, compoundYield 144.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of tert-butyl(3S, 5R)-3-[{[1-(3-ethoxy-3-oxopropyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (260 mg) in ethanol (5 ml) was added 2M aqueous sodium hydroxide solution (1.06 ml), and the mixture was stirred at room temperature for 3 days. The reaction mixture was 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, N-hydroxy acetamidine (47 mg), 1H-benzotriazol-1-ol (79 mg) and N,N-diisopropylethylamine (217 μl) were dissolved in DMF (5 ml), WSC.HCl (121 mg) was added and the mixture was stirred at 60° C. for 2 hr. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with aqueous sodium bicarbonate and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in toluene (15 ml), and the mixture was refluxed under heating for 15 hr. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure. The residue was subjected to basic silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (7:3) was concentrated under reduced pressure to give the object product (191 mg).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionThe residue, N-hydroxy acetamidine (47 mg), 1H-benzotriazol-1-ol (79 mg) and N,N-diisopropylethylamine (217 μl) were dissolved in DMF (5 ml)
  6. additionWSC.HCl (121 mg) was added
  7. stirringthe mixture was stirred at 60° C. for 2 hr
  8. concentrationThe reaction mixture was concentrated under reduced pressure
  9. additionthe residue was diluted with aqueous sodium bicarbonate
  10. extractionextracted with ethyl acetate
  11. washThe extract was washed with saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customThe solvent was evaporated under reduced pressure
  14. dissolutionThe residue was dissolved in toluene (15 ml)
  15. temperaturethe mixture was refluxed
  16. temperatureunder heating for 15 hr
  17. temperatureThe reaction mixture was cooled to room temperature
  18. concentrationconcentrated under reduced pressure
  19. washa fraction eluted with ethyl acetate-hexane (7:3)
  20. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-9867e85d7e0b43a3991aa5710d62a278
Source dataset
uspto-grants-2014_03
Patent number
US08664380B2

Reaction notes

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