Benzyl Alcohol → [5-Oxo-1-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)pyrrolidin-3-yl]carbamic acid benzyl ester

HRID 1847009Notes

Reaction equation

HRID 1847009 reaction equation
[O:1]=[C:2]1[N:6]([C:7]2[CH:8]=[CH:9][C:10]3[O:11][CH2:12][C:13](=[O:17])[NH:14][C:15]=3[N:16]=2)[CH2:5][CH:4](C(O)=O)[CH2:3]1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:28])C=CC=CC=1.C([N:40]([CH2:43]C)CC)C.[CH2:45]([OH:52])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>C1C=CC=CC=1>[CH2:45]([O:52][C:43](=[O:28])[NH:40][CH:4]1[CH2:3][C:2](=[O:1])[N:6]([C:7]2[CH:8]=[CH:9][C:10]3[O:11][CH2:12][C:13](=[O:17])[NH:14][C:15]=3[N:16]=2)[CH2:5]1)[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 867249395-Oxo-1-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)pyrrolidin-3-carboxylic acid

Product 1

HCID 86724940[5-Oxo-1-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)pyrrolidin-3-yl]carbamic acid benzyl esterYield 47%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A mixture of 5-oxo-1-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)pyrrolidin-3-carboxylic acid (764 mg, 2.76 mmol), diphenyl phosphoryl azide (0.891 ml, 4.13 mmol), triethylamine (0.626 ml, 4.49 mmol) and benzene (35 ml) was heated under reflux for 3 hours. Benzyl alcohol (21 ml) was added to the reaction solution, which was further heated under reflux overnight. After cooling, the insoluble material was removed by filtration, the filtrate was diluted with ethyl acetate, washed with a saturated sodium hydrogen carbonate aqueous solution and saturated sodium chloride solution, dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate and chloroform/methanol) to yield 496 mg (47%) of the title compound in the form of a light yellow solid.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 3 hours
  3. temperaturewas further heated
  4. temperatureunder reflux overnight
  5. temperatureAfter cooling
  6. customthe insoluble material was removed by filtration
  7. additionthe filtrate was diluted with ethyl acetate
  8. washwashed with a saturated sodium hydrogen carbonate aqueous solution and saturated sodium chloride solution
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customthe solvent was removed under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate and chloroform/methanol)

Sources & evidence

ORD record
ord-3f6bd7e7d80f4d6b8140f8aed81ac028
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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