Hydroxyamine hydrochloride → tert-butyl (6R,7R)-7-(3,4-dichlorophenyl)-6-{[2-oxo-3-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)pyridin-1(2H)-yl]methyl}-1,4-oxazepane-4-carboxylate

HRID 1022605Notes

Reaction equation

HRID 1022605 reaction equation
[C:1](=[O:4])([O-])[OH:2].[Na+].Cl.NO.[C:9]([C:11]1[C:12](=[O:40])[N:13]([CH2:17][C@H:18]2[C@H:24]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([Cl:32])[CH:26]=3)[O:23][CH2:22][CH2:21][N:20]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:19]2)[CH:14]=[CH:15][CH:16]=1)#[N:10].C1(C2CCCCCCCCCC=2)CCCCCCCCN[N:42]=1>CS(C)=O.O.C1COCC1>[Cl:32][C:27]1[CH:26]=[C:25]([C@@H:24]2[O:23][CH2:22][CH2:21][N:20]([C:33]([O:35][C:36]([CH3:37])([CH3:39])[CH3:38])=[O:34])[CH2:19][C@H:18]2[CH2:17][N:13]2[CH:14]=[CH:15][CH:16]=[C:11]([C:9]3[NH:42][C:1](=[O:4])[O:2][N:10]=3)[C:12]2=[O:40])[CH:30]=[CH:29][C:28]=1[Cl:31]

Participants

8

Reactant 4

HCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 536302743-(Cycloundecen-1-yl)-1,2-diazacycloundec-2-eneHCID 66975537tert-butyl (6R,7R)-6-[(3-cyano-2-oxopyridin-1(2H)-yl)methyl]-7-(3,4-dichlorophenyl)-1,4-oxazepane-4-carboxylate

Product 1

HCID 136340695tert-butyl (6R,7R)-7-(3,4-dichlorophenyl)-6-{[2-oxo-3-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)pyridin-1(2H)-yl]methyl}-1,4-oxazepane-4-carboxylateYield 72.6%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

Sodium hydrogen carbonate (829 mg, 9.87 mmol) and hydroxylamine hydrochloride (686 mg, 9.87 mmol) were added to a solution of tert-butyl (6R,7R)-6-[(3-cyano-2-oxopyridin-1(2H)-yl)methyl]-7-(3,4-dichlorophenyl)-1,4-oxazepane-4-carboxylate (590 mg, 1.23 mmol) in DMSO (4 mL), and the mixture was stirred at 80° C. for 5 hr. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was diluted with THF (10 mL), diazabicycloundecene (0.184 mL, 1.23 mmol) and carbonyl-1,1′-bisimidazole (299 mg, 1.85 mmol) were added, and the mixture was stirred at 70° C. for 2 hr. The reaction mixture was concentrated under reduced pressure, and the residue was acidified with 1 N hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and recrystallized from ethanol-hexane to give the title compound (480 mg, 0.893 mmol, 72.6%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. additionwere added
  6. stirringthe mixture was stirred at 70° C. for 2 hr
  7. concentrationThe reaction mixture was concentrated under reduced pressure
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe extract was washed with brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography
  13. customrecrystallized from ethanol-hexane

Sources & evidence

ORD record
ord-a66d52cb102048e0b228a4c272522d6e
Source dataset
uspto-grants-2014_05
Patent number
US08722662B2

Reaction notes

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