Acetic Acid → 1-[5-(5-aminopyridin-2-yloxy)-4-chloro-2-fluorophenyl]-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one

HRID 1090983Notes

Reaction equation

HRID 1090983 reaction equation
[Cl:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][N:10]=2)=[CH:6][C:5]([N:18]2[C:22](=[O:23])[N:21]([CH:24]([F:26])[F:25])[C:20]([CH3:27])=[N:19]2)=[C:4]([F:28])[CH:3]=1.C(O)(=O)C.O1CCCC1.O>C(OCC)C.[Fe]>[NH2:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][C:7]2[C:2]([Cl:1])=[CH:3][C:4]([F:28])=[C:5]([N:18]3[C:22](=[O:23])[N:21]([CH:24]([F:25])[F:26])[C:20]([CH3:27])=[N:19]3)[CH:6]=2)=[N:10][CH:11]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 8028TetrahydrofuranHCID 199122211-[4-chloro-2-fluoro-5-(5-nitropyridin-2-yloxy) phenyl]-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one

Product 1

HCID 199122051-[5-(5-aminopyridin-2-yloxy)-4-chloro-2-fluorophenyl]-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-oneYield 91.5%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 3283Diethyl EtherSolvent

Procedure

Iron filings (3.6 g, 0.064 mole) were added slowly to a stirred mixture of 7.0 g (0.017 mole) of 1-[4-chloro-2-fluoro-5-(5-nitropyridin-2-yloxy) phenyl]-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one, 25 mL of glacial acetic acid, 12 mL of tetrahydrofuran, and 5 mL of water. The reaction mixture was stirred at room temperature for three hours and was then diluted with 20 mL of diethyl ether. The mixture was filtered through a pad of Celite® filter aid, and the filtrate was stored at 5° C. to 10° C. for approximately 18 hours. The filtrate was neutralized by the addition of solid sodium bicarbonate and water. The organic phase was separated from the aqueous phase. The aqueous phase was extracted several times with diethyl ether, and the extracts were combined with the organic phase. The combined organic phase was washed first with water, then with an aqueous, saturated sodium chloride solution. The organic phase was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to yield 6.0 g of 1-[5-(5-aminopyridin-2-yloxy)-4-chloro-2-fluorophenyl]-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one as a solid.

Workup

  1. filtrationThe mixture was filtered through a pad of Celite®
  2. filtrationfilter aid
  3. waitthe filtrate was stored at 5° C. to 10° C. for approximately 18 hours
  4. additionThe filtrate was neutralized by the addition of solid sodium bicarbonate and water
  5. customThe organic phase was separated from the aqueous phase
  6. extractionThe aqueous phase was extracted several times with diethyl ether
  7. washThe combined organic phase was washed first with water
  8. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customThe filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-eedac705824c41e185847fb2f77ff274
Source dataset
uspto-grants-1992_01
Patent number
US05084085

Reaction notes

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