Methanol → HCID 178509502, compound

HRID 623833Notes

Reaction equation

HRID 623833 reaction equation
[NH:1]1[CH:5]=[N:4][C:3]([C:6]2[CH:7]=[C:8]([CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=2)[C:9]([NH2:11])=O)=[N:2]1.O=P(Cl)(Cl)Cl.CO.ClCCl>CN(C=O)C>[NH:1]1[CH:5]=[N:4][C:3]([C:6]2[CH:7]=[C:8]([CH:12]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:14]=2)[C:9]#[N:11])=[N:2]1

Participants

6

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 24813Phosphorus oxychlorideHCID 178513572HCID 178513572, compound

Product 1

HCID 178509502HCID 178509502, compoundYield 107.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

In 3-neck 50 mL round-bottomed flask, 3-(1H-1,2,4-triazol-3-yl)-5-(trifluoromethyl)benzamide (0.5 g, 1 eq.) and POCl3 (2.0 mL, 4 eq.) was dissolved in DMF (15 mL, 15 Vol) and reaction mixture was stirred at 25° C. for 1-2 hr. 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=0.35 and Product Rf=0.45. Reaction mixture was concentrated under reduced pressure to afford 0.1.2 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 1.5% to 2.0% Methanol in dichloromethane. Compound started eluting with 1.5% Methanol in dichloromethane. Fraction containing such TLC profile was collected together to obtain pure 3-(1H-1,2,4-triazol-3-yl)-5-(trifluoromethyl)benzonitrile (500 mg), Yield (60%); Mass: (ES+) 238.1 (M+1).

Workup

  1. customreaction mixture
  2. customReaction mixture
  3. concentrationwas concentrated under reduced pressure
  4. customto afford 0.1.2 g of crude compound
  5. customThe crude reaction mixture
  6. customwas purified by column chromatography
  7. washstarted eluting in Methanol in gradient manner
  8. customstarting with fraction collection (25-mL fractions) from 1.5% to 2.0% Methanol in dichloromethane
  9. washCompound started eluting with 1.5% Methanol in dichloromethane
  10. additionFraction containing such TLC profile
  11. customwas collected together

Sources & evidence

ORD record
ord-377b2f8e24f94ca39ab0b455ca296f3f
Source dataset
uspto-grants-2016_04
Patent number
US09303000B2

Reaction notes

Loading…