Water → HCID 136340701, compound

HRID 1022666Notes

Reaction equation

HRID 1022666 reaction equation
[C:1](=[O:4])([O-])[OH:2].[Na+].Cl.[NH2:7]O.[C:9]([C:11]1[C:12](=[O:39])[N:13]([CH:17]2[CH:23]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([Cl:31])[CH:25]=3)[O:22][CH2:21][CH2:20][N:19]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:18]2)[CH:14]=[CH:15][CH:16]=1)#[N:10].O>CS(C)=O>[Cl:31][C:26]1[CH:25]=[C:24]([CH:23]2[O:22][CH2:21][CH2:20][N:19]([C:32]([O:34][C:35]([CH3:36])([CH3:38])[CH3:37])=[O:33])[CH2:18][CH:17]2[N:13]2[CH:14]=[CH:15][CH:16]=[C:11]([C:9]3[NH:7][C:1](=[O:4])[O:2][N:10]=3)[C:12]2=[O:39])[CH:29]=[CH:28][C:27]=1[Cl:30]

Participants

6

Reactant 4

HCID 962WaterHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 66975256HCID 66975256, compound

Product 1

HCID 136340701HCID 136340701, compoundYield 49.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

Sodium hydrogen carbonate (145 mg) and hydroxylamine monohydrochloride (120 mg) were added to a solution of tert-butyl (6RS,7SR)-6-(3-cyano-2-oxopyridin-1(2H)-yl)-7-(3,4-dichlorophenyl)-1,4-oxazepane-4-carboxylate (100 mg) in DMSO (4 mL), and the mixture was stirred at 80° C. overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in THF (10 mL), diazabicycloundecene (0.032 mL) and CDI (52 mg) were added, and the mixture was heated under reflux for 1 hr. To the reaction mixture was added 1 N aqueous hydrochloric acid solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (56 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionThe residue was dissolved in THF (10 mL)
  6. additiondiazabicycloundecene (0.032 mL) and CDI (52 mg) were added
  7. temperaturethe mixture was heated
  8. temperatureunder reflux for 1 hr
  9. additionTo the reaction mixture was added 1 N aqueous hydrochloric acid solution
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe extract was washed with water and brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customThe solvent was evaporated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-d3ecdd8626474e619e69a0ec6e5b9898
Source dataset
uspto-grants-2014_05
Patent number
US08722662B2

Reaction notes

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