3-Carbethoxy-2-piperidone → Ethyl 3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylate

HRID 1398146Notes

Reaction equation

HRID 1398146 reaction equation
O=[C:2]1[CH:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:6][CH2:5][CH2:4][NH:3]1.F[B-](F)(F)F.C[O+](C)C.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH:31]=[CH:32][C:33]=1[C:34]1[O:38][C:37]([CH3:39])=[N:36][CH:35]=1)[C:27]([NH:29][NH2:30])=O>C(#N)C>[CH3:22][O:23][C:24]1[CH:25]=[C:26]([C:27]2[N:3]3[CH2:4][CH2:5][CH2:6][CH:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:2]3=[N:30][N:29]=2)[CH:31]=[CH:32][C:33]=1[C:34]1[O:38][C:37]([CH3:39])=[N:36][CH:35]=1

Participants

5

Reactant 3

HCID 977733-Carbethoxy-2-piperidoneHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 666079613-Methoxy-4-(2-methyloxazol-5-yl)benzohydrazide

Product 1

HCID 66608236Ethyl 3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylateYield 37.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of ethyl 2-oxo-3-piperidinecarboxylate (34.6 g), trimethyloxonium tetrafluoroborate (95%, 31.5 g) and acetonitrile (600 mL) was stirred at room temperature for 16 hr. 3-Methoxy-4-(2-methyl-1,3-oxazol-5-yl)benzohydrazide (50.0 g) was added to the reaction mixture at room temperature, and the mixture was heated under reflux for 24 hr, allowed to cool to room temperature and concentrated under reduced pressure. Saturated aqueous sodium hydrogen carbonate solution was added to the residue, the insoluble material was filtered off through celite, and the filtrate was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was crystallized from methanol/ethyl acetate to give the title compound (29.0 g).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 24 hr
  3. temperatureto cool to room temperature
  4. concentrationconcentrated under reduced pressure
  5. additionSaturated aqueous sodium hydrogen carbonate solution was added to the residue
  6. filtrationthe insoluble material was filtered off through celite
  7. extractionthe filtrate was extracted with ethyl acetate
  8. washThe extract was washed with saturated brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. customthe solvent was evaporated under reduced pressure
  11. customThe residue was crystallized from methanol/ethyl acetate

Sources & evidence

ORD record
ord-4ff5928e71274776aa4a6ec9f553a175
Source dataset
uspto-grants-2014_12
Patent number
US08901309B2

Reaction notes

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