[(6-{(4S)-4-[(tert-Butoxycarbonyl)amino]-2-oxopyrrolidin-1-yl}-2-nitropyridin-3-yl)oxy]acetic acid ethyl ester → [(3S)-5-Oxo-1-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)pyrrolidin-3-yl]carbamic acid tert-butyl ester

HRID 1847012Notes

Reaction equation

HRID 1847012 reaction equation
C(O[C:4](=[O:30])[CH2:5][O:6][C:7]1[C:8]([N+:27]([O-])=O)=[N:9][C:10]([N:13]2[CH2:17][C@@H:16]([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][C:14]2=[O:26])=[CH:11][CH:12]=1)C>C(O)(=O)C>[C:22]([O:21][C:19](=[O:20])[NH:18][C@H:16]1[CH2:15][C:14](=[O:26])[N:13]([C:10]2[CH:11]=[CH:12][C:7]3[O:6][CH2:5][C:4](=[O:30])[NH:27][C:8]=3[N:9]=2)[CH2:17]1)([CH3:25])([CH3:23])[CH3:24]

Participants

3

Reactant 1

HCID 86724942[(6-{(4S)-4-[(tert-Butoxycarbonyl)amino]-2-oxopyrrolidin-1-yl}-2-nitropyridin-3-yl)oxy]acetic acid ethyl ester

Product 1

HCID 86724943[(3S)-5-Oxo-1-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)pyrrolidin-3-yl]carbamic acid tert-butyl esterYield 98%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
85 °C

Procedure

Reduced iron (150 mg, 2.69 mmol) was added to a solution of [(6-{(4S)-4-[(tert-butoxycarbonyl)amino]-2-oxopyrrolidin-1-yl}-2-nitropyridin-3-yl)oxy]acetic acid ethyl ester (380 mg, 0.895 mmol) in acetic acid (3.8 ml) and the mixture was stirred at 85° C. for 1.5 hours. After cooling, the insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane, a saturated sodium hydrogen carbonate aqueous solution was added thereto and the mixture was stirred for 10 minutes. The solvent was removed under reduced pressure and the obtained residue was purified by silica gel column chromatography (chloroform/methanol) to yield 305 mg (98%) of the title compound in the form of a colorless solid.

Workup

  1. temperatureAfter cooling
  2. customthe insoluble material was removed by filtration
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in dichloromethane
  5. additiona saturated sodium hydrogen carbonate aqueous solution was added
  6. stirringthe mixture was stirred for 10 minutes
  7. customThe solvent was removed under reduced pressure
  8. customthe obtained residue was purified by silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-3bc5a3ce871a40b4ab7982456c5f73cd
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

Loading…