Hydrochloric Acid → 4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorothiophenol

HRID 257384Notes

Reaction equation

HRID 257384 reaction equation
Cl.[Sn](Cl)Cl.[F:5][CH:6]([F:25])[N:7]1[C:11](=[O:12])[N:10]([C:13]2[CH:18]=[CH:17][C:16]([S:19](Cl)(=O)=O)=[CH:15][C:14]=2[F:23])[N:9]=[C:8]1[CH3:24].[Cl-].[Na+]>C(O)(=O)C>[F:25][CH:6]([F:5])[N:7]1[C:11](=[O:12])[N:10]([C:13]2[CH:18]=[CH:17][C:16]([SH:19])=[CH:15][C:14]=2[F:23])[N:9]=[C:8]1[CH3:24]

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 5234Sodium ChlorideHCID 24479Stannous ChlorideHCID 189810494-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenylsulfonyl chloride

Product 1

HCID 189810404-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorothiophenolYield 60.7%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
85 °C

Procedure

Gaseous hydrogen chloride was bubbled into a mixture of 3.29 g (0.0146 mole) of tin(II) chloride in 40 mL of acetic acid for about five minutes, causing it to become a clear solution. This solution was then heated to 85° C., and a hot solution of 1.66 g (0.00485 mole) of 4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenylsulfonyl chloride was added to the first solution. This reaction mixture was heated at 85° C. for 45 minutes. After cooling to room temperature, the resulting yellow solution was poured into 120 mL of hydrochloric acid. To this mixture was added 100 mL of a saturated aqueous solution of sodium chloride, and the resulting mixture was extracted with ethyl acetate, but the layers did not separate. The addition of a saturated aqueous solution of sodium chloride did effect a partial separation. The aqueous layer was extracted two more times with ethyl acetate, and all extracts were combined. After evaporation of the solvent under reduced pressure, the residue retained an odor of hydrochloric acid. Water was added to the residue, and this mixture was extracted three times with ethyl acetate. The combined extracts were washed with water, dried over anhydrous magnesium sulfate, and filtered. Following evaporation of the solvent under reduced pressure, the yellow residue that remained was dried under vacuum. This dried residue was placed on a column of silica gel and eluted with methylene chloride/ethyl acetate (2:1). After being dried under vacuum for several hours, 0.81 g of 4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorothiophenol was isolated as a yellow syrup. The NMR spectrum was consistent with the proposed structure. This reaction was repeated to obtain additional product for subsequent reactions.

Workup

  1. temperatureThis reaction mixture was heated at 85° C. for 45 minutes
  2. temperatureAfter cooling to room temperature
  3. extractionthe resulting mixture was extracted with ethyl acetate
  4. customthe layers did not separate
  5. additionThe addition of a saturated aqueous solution of sodium chloride
  6. customa partial separation
  7. extractionThe aqueous layer was extracted two more times with ethyl acetate
  8. customAfter evaporation of the solvent under reduced pressure
  9. additionWater was added to the residue
  10. extractionthis mixture was extracted three times with ethyl acetate
  11. washThe combined extracts were washed with water
  12. dry with materialdried over anhydrous magnesium sulfate
  13. filtrationfiltered
  14. customevaporation of the solvent under reduced pressure
  15. customthe yellow residue that remained was dried under vacuum
  16. washeluted with methylene chloride/ethyl acetate (2:1)
  17. customAfter being dried under vacuum for several hours

Sources & evidence

ORD record
ord-993b179f1cb94a40b11539b92d84aad9
Source dataset
uspto-grants-1993_11
Patent number
US05262390

Reaction notes

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