Methanol → tert-Butyl [(3R)-5-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl}pyrrolidin-3-yl]carbamate

HRID 1847077Notes

Reaction equation

HRID 1847077 reaction equation
C(OC[N:10]1[C:15]2[CH:16]=[C:17]([N:20]3[C:24](=[O:25])[CH2:23][C@@H:22]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:21]3)[CH:18]=[CH:19][C:14]=2[O:13][CH2:12][C:11]1=[O:34])C1C=CC=CC=1.C([O-])=O.[NH4+].CO>[Pd].O1CCCC1>[O:25]=[C:24]1[N:20]([C:17]2[CH:18]=[CH:19][C:14]3[O:13][CH2:12][C:11](=[O:34])[NH:10][C:15]=3[CH:16]=2)[CH2:21][C@H:22]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:31])([CH3:30])[CH3:32])[CH2:23]1

Participants

6

Reactant 3

HCID 887MethanolHCID 2723923Ammonium formate2×HCID 86725000tert-Butyl [(3R)-1-{4-[(Benzyloxy)methyl]-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl}-5-oxopyrrolidin-3-yl]carbamate

Product 1

HCID 86725001tert-Butyl [(3R)-5-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl}pyrrolidin-3-yl]carbamateYield 93%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of tert-butyl [(3R)-1-{4-[(benzyloxy)methyl]-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl}-5-oxopyrrolidin-3-yl]carbamate (15.0 g, 32.1 mmol), ammonium formate (6.93 g, 110 mmol), methanol (250 ml) and tetrahydrofuran (93 ml) was added 10% Palladium on carbon (50% wet, 15.0 g) and the mixture was heated under reflux for 1 hour on an oil bath at 100° C. Ammonium formate (7.00 g, 111 mmol) was added and the mixture was further heated under reflux for 1 hour. Subsequently the catalyst was removed by filtration and the residue was washed thoroughly with a mixed solvent of chloroform-methanol (1:1). The filtrate and washings were combined to remove the solvent under reduced pressure and the residue was suspended in water from which the insoluble material was removed by filtration. The residue was washed with water and dried with heating under reduced pressure. 10.33 g (93%) of the title compound was obtained in the form of a white solid.

Workup

  1. temperaturethe mixture was heated
  2. temperaturethe mixture was further heated
  3. temperatureunder reflux for 1 hour
  4. customSubsequently the catalyst was removed by filtration
  5. washthe residue was washed thoroughly with a mixed solvent of chloroform-methanol (1:1)
  6. customto remove the solvent under reduced pressure
  7. customwas removed by filtration
  8. washThe residue was washed with water
  9. customdried
  10. temperaturewith heating under reduced pressure

Sources & evidence

ORD record
ord-c19d5e4eb7f74c6399053142b3018d7d
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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