Hydrochloric Acid → HCID 19912213, compound

HRID 1090988Notes

Reaction equation

HRID 1090988 reaction equation
[Cl:1][C:2]1[CH:18]=[C:17]([F:19])[C:16]([N:20]2[C:24](=[O:25])[N:23]([CH:26]([F:28])[F:27])[C:22]([CH3:29])=[N:21]2)=[CH:15][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]([O:13]C)=[O:12])=[CH:7][CH:6]=1.ClC1C=C(F)C(N2C(=O)N(C(F)F)C(C)=N2)=CC=1OC1C=CC(C(OCC)=O)=CC=1.[OH-].[Na+].Cl>O1CCCC1.O.C(O)C>[Cl:1][C:2]1[CH:18]=[C:17]([F:19])[C:16]([N:20]2[C:24](=[O:25])[N:23]([CH:26]([F:28])[F:27])[C:22]([CH3:29])=[N:21]2)=[CH:15][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]([OH:13])=[O:12])=[CH:7][CH:6]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 19912204methyl 4-[2-chloro-4-fluoro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenoxy]-phenylcarboxylateHCID 19912232ethyl 4-[2-chloro-4-fluoro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenoxy]phenylcarboxylate

Product 1

HCID 19912213HCID 19912213, compoundYield 143.9%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred mixture of 1.8 g (0.0042 mole) of methyl 4-[2-chloro-4-fluoro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4 -triazol-1-yl)phenoxy]-phenylcarboxylate and 1.3 g (0.0029 mole) of ethyl 4-[2-chloro-4-fluoro-5-(4-difluoromethyl-4,5-dihydro -3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenoxy]phenylcarboxylate (prepared by the method of Step B using ethanol in place of methanol) in 20 mL of tetrahydrofuran was added a solution of 0.58 g (0.014) of sodium hydroxide in 30 mL of water. The reaction mixture was heated at 50° C. for 1.5 hour, then was stirred at room temperature for approximately 18 hours. The mixture was again heated at 50° C. for two hours and then was allowed to cool. The solvent was removed from the mixture by evaporation under reduced pressure leaving a residue. The residue was stirred in a 2N hydrochloric acid solution, and the resultant mixture was extracted successively with diethyl ether and ethyl acetate. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate concentrated under reduced pressure to give a solid residue. The residue was purified by column chromatography on silica gel, eluting with methylene chloride:methanol (95:5) to give 2.5 g of 4-[2-chloro-4-fluoro-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo 1H-1,2,4-triazol-1-yl)phenoxy]phenylcarboxylic acid as a solid, m.p. 184°-185° C.

Workup

  1. customprepared by the method of Step B
  2. temperatureThe mixture was again heated at 50° C. for two hours
  3. temperatureto cool
  4. customThe solvent was removed from the mixture by evaporation under reduced pressure
  5. customleaving a residue
  6. extractionthe resultant mixture was extracted successively with diethyl ether and ethyl acetate
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate concentrated under reduced pressure
  10. customto give a solid residue
  11. customThe residue was purified by column chromatography on silica gel
  12. washeluting with methylene chloride:methanol (95:5)

Sources & evidence

ORD record
ord-daa531dfd6ac4faeb71c8feb4057292b
Source dataset
uspto-grants-1992_01
Patent number
US05084085

Reaction notes

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