1,1'-Carbonyldiimidazole → tert-butyl (6R,7R)-7-(4-chloro-3-fluorophenyl)-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 1022635Notes

Reaction equation

HRID 1022635 reaction equation
[C:1](=[O:4])([O-])[OH:2].[Na+].Cl.NO.[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C@@H:16]2[O:22][CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18][C@H:17]2[CH2:30][N:31]2[CH:36]=[CH:35][CH:34]=[C:33]([C:37]#[N:38])[C:32]2=[O:39])=[CH:12][C:11]=1[F:40].C1(C2CCCCCCCCCC=2)CCCCCCCCN[N:42]=1.C(N1C=CN=C1)(N1C=CN=C1)=O>CS(C)=O.O>[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C@@H:16]2[O:22][CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])[CH2:18][C@H:17]2[CH2:30][N:31]2[CH:36]=[CH:35][CH:34]=[C:33]([C:37]3[NH:42][C:1](=[O:4])[O:2][N:38]=3)[C:32]2=[O:39])=[CH:12][C:11]=1[F:40]

Participants

8

Reactant 5

HCID 682631,1'-CarbonyldiimidazoleHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 536302743-(Cycloundecen-1-yl)-1,2-diazacycloundec-2-eneHCID 66976171HCID 66976171, compound

Product 1

HCID 136340698tert-butyl (6R,7R)-7-(4-chloro-3-fluorophenyl)-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 93.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

Sodium hydrogen carbonate (2.53 g, 30.14 mmol) and hydroxylamine monohydrochloride (2.094 g, 30.14 mmol) were added to a solution of tert-butyl (6R,7R)-7-(4-chloro-3-fluorophenyl)-6-[(3-cyano-2-oxopyridin-1(2H)-yl)methyl]-1,4-oxazepane-4-carboxylate (1.74 g, 3.77 mmol) in DMSO (4 mL), and the mixture was stirred at 80° C. overnight. To the reaction mixture was added 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 dissolved in THF (15 mL), diazabicycloundecene (0.564 mL, 3.77 mmol) and 1,1′-carbonyldiimidazole (0.917 g, 5.66 mmol) were added, and the mixture was heated under reflux for 2 hr. The reaction mixture was concentrated under reduced pressure, 1 N hydrochloric acid was added to the residue, 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 to give the title compound (1.826 g, 3.51 mmol, 93%).

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. dissolutionThe residue was dissolved in THF (15 mL)
  6. temperaturethe mixture was heated
  7. temperatureunder reflux for 2 hr
  8. concentrationThe reaction mixture was concentrated under reduced pressure, 1 N hydrochloric acid
  9. additionwas added to the residue
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe extract was washed with brine
  12. dry with materialdried over anhydrous sodium sulfate
  13. customThe solvent was evaporated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-9fb2df42b3214b4bb387231a7b869d9d
Source dataset
uspto-grants-2014_05
Patent number
US08722662B2

Reaction notes

Loading…