Formic Acid → HCID 178513572, compound

HRID 623832Notes

Reaction equation

HRID 623832 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1)[C:7]([NH2:9])=O)(=S)[NH2:2].[OH2:17].[NH2:18][NH2:19].[C:20](OCC)(=O)C.CCCCCC.C(O)=O>CN(C=O)C.ClCCl.CO>[NH:18]1[CH:20]=[N:2][C:1]([C:4]2[CH:5]=[C:6]([CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=2)[C:7]([NH2:9])=[O:17])=[N:19]1

Participants

8

Reactant 4

HCID 284Formic AcidHCID 24654Hydrazine hydrate (1:1)HCID 21226206Ethyl acetate hexaneHCID 86672070HCID 86672070, compound

Product 1

HCID 178513572HCID 178513572, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

In 3-neck 100 mL round-bottomed flask, 3-carbamothioyl-5-(trifluoromethyl)benzamide (3.0 g, 1 eq.) was dissolved in DMF (30 mL, 10 Vol) and dropwise added hydrazine hydrate (1.27 mL, 2.0 eq.) and reaction mixture was stirred at room temperature for 1-2 h. The progress of the reaction was followed by TLC analysis on silica gel with ethyl acetate:hexane (2:8) mobile phase and visualization with UV, SM Rf=0.35 and Product Rf=0.15. Then formic acid (5 mL, 5 vol) was added and stirred for 1 h at the same temperature. Then temperature increased to 90° C. and maintained for 10-12 hrs. The progress of the reaction was followed by TLC analysis on silica gel with 10% methanol: dichloromethane as mobile phase and visualization with UV, SM Rf=0.30 and Product Rf=0.20. Reaction mixture was quenched into the ice-water slurry (300 mL) and extracted in the ethyl acetate (100 mL×3). Organic layer was washed with sodium bicarbonate solution (100×3 mL) followed by drying using anhydrous sodium sulphate. Organic layer was concentrated under reduced pressure to afford 3.0 g of crude compound. The crude reaction mixture was purified by column chromatography using silica 60/120 using methanol: dichloromethane as mobile phase. The column (5×10 cm) was packed in dichloromethane and started eluting in Methanol in gradient manner starting with fraction collection (25 mL fractions) from 3-5% methanol in dichloromethane. Compound started eluting with 3% methanol in dichloromethane. Fraction containing such TLC profile was collected together to obtain pure 3-(1H-1,2,4-triazol-3-yl)-5-(trifluoromethyl)benzamide (1.1 g), Yield (36.0%); Mass: (ES+) 257.14 (M+1).

Workup

  1. stirringstirred for 1 h at the same temperature
  2. temperatureThen temperature increased to 90° C.
  3. temperaturemaintained for 10-12 hrs
  4. customReaction mixture
  5. customwas quenched into the ice-water slurry (300 mL)
  6. extractionextracted in the ethyl acetate (100 mL×3)
  7. washOrganic layer was washed with sodium bicarbonate solution (100×3 mL)
  8. customby drying
  9. concentrationOrganic layer was concentrated under reduced pressure
  10. customto afford 3.0 g of crude compound
  11. customThe crude reaction mixture
  12. customwas purified by column chromatography
  13. washstarted eluting in Methanol in gradient manner
  14. customstarting with fraction collection (25 mL fractions) from 3-5% methanol in dichloromethane
  15. washCompound started eluting with 3% methanol in dichloromethane
  16. additionFraction containing such TLC profile
  17. customwas collected together

Sources & evidence

ORD record
ord-e46d6e53effe48df9e13e50eb4b2a73d
Source dataset
uspto-grants-2016_04
Patent number
US09303000B2

Reaction notes

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