Water → HCID 58243498, compound

HRID 389153Notes

Reaction equation

HRID 389153 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:12][C:13]([CH3:31])([C:15]2[N:19]([CH3:20])[C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:27]([F:30])([F:29])[F:28])=[N:17][N:16]=2)[CH3:14])=[C:6]([CH:11]=1)[C:7]([NH:9][NH2:10])=[O:8].C(N(CC)CC)C.Cl[C:40](=O)[C:41]([O:43][CH2:44][CH3:45])=[O:42].O>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:12][C:13]([CH3:31])([C:15]2[N:19]([CH3:20])[C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:27]([F:29])([F:28])[F:30])=[N:17][N:16]=2)[CH3:14])=[C:6]([C:7]2[O:8][C:40]([C:41]([O:43][CH2:44][CH3:45])=[O:42])=[N:10][N:9]=2)[CH:11]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 20884Ethoxalyl chlorideHCID 58243744HCID 58243744, compound

Product 1

HCID 58243498HCID 58243498, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

5-chloro-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)benzohydrazide (782 mg) was dissolved in THF (10 ml), and triethylamine (0.510 ml) was added thereto, followed by ice-cooling. Ethyl chloro(oxo)acetate (0.200 ml) was added thereto, followed by stirring at room temperature overnight. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was washed with diisopropylether. The resulting solid (650 mg) was dissolved in dichloromethane (10 ml), and pyridine (0.385 ml) was added thereto, followed by cooling to −78° C. Trifluoromethanesulfonic anhydride (0.385 ml) was added to the reaction solution and was elevated to room temperature, followed by stirring for 30 minutes. Saturated aqueous sodium bicarbonate was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:1). The resulting solid was washed with diisopropylether, to obtain, as a yellowish white solid, ethyl 5-[5-chloro-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)phenyl]-1,3,4-oxadiazole-2-carboxylate (240 mg).

Workup

  1. temperaturecooling
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. washThe residue was washed with diisopropylether
  6. dissolutionThe resulting solid (650 mg) was dissolved in dichloromethane (10 ml)
  7. additionpyridine (0.385 ml) was added
  8. temperatureby cooling to −78° C
  9. additionTrifluoromethanesulfonic anhydride (0.385 ml) was added to the reaction solution
  10. customwas elevated to room temperature
  11. stirringby stirring for 30 minutes
  12. additionSaturated aqueous sodium bicarbonate was added to the reaction solution
  13. extractionfollowed by extraction with ethyl acetate
  14. washThe organic layer was washed with saturated brine
  15. dry with materialdried over anhydrous magnesium sulfate
  16. customthe solvent was then evaporated under reduced pressure
  17. customThe resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:1)
  18. washThe resulting solid was washed with diisopropylether

Sources & evidence

ORD record
ord-7918ad162b9941fb8912039567aa17bf
Source dataset
uspto-grants-2013_02
Patent number
US08377923B2

Reaction notes

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