Triethylamine → 2-Methyl-6-trifluoromethylnicotinic acid 4-oxobicyclo[3.2.1]oct-2-en-2-yl ester

HRID 2180900Notes

Reaction equation

HRID 2180900 reaction equation
[CH3:1][C:2]1[N:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[CH2:15](N(CC)CC)C.CN([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27]N=1)C.[C:31](Cl)(=[O:35])[C:32](Cl)=O>CN(C)C=O.C(Cl)Cl>[O:35]=[C:31]1[CH:32]2[CH2:15][CH:29]([CH2:30][CH2:25]2)[C:28]([O:5][C:4](=[O:6])[C:3]2[CH:7]=[CH:8][C:9]([C:11]([F:14])([F:12])[F:13])=[N:10][C:2]=2[CH3:1])=[CH:27]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 218852-DimethylaminopyridineHCID 65578Oxalyl chlorideHCID 27756832-Methyl-6-(trifluoromethyl)nicotinic acid

Product 1

HCID 691301142-Methyl-6-trifluoromethylnicotinic acid 4-oxobicyclo[3.2.1]oct-2-en-2-yl esterYield 100%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

The 2-methyl-6-trifluoromethyl-nicotinic acid (2.0 g, 0.0098 mol) obtained is dissolved in 20 ml of oxalyl chloride. Three drops of dimethylformamide are added and the mixture is refluxed for 1 hour. The mixture is then concentrated using a rotary evaporator and the residue (2-methyl-6-trifluoromethyl-nicotinoyl chloride) is taken up in 30 ml of methylene chloride. At 0° C., 2.7 ml (0.0196 mol) of triethylamine and 0.12 g (0.00098 mol) of dimethylaminopyridine are added, and then 1.49 g (0.0108 mol) of bicyclo[3.2.1]oct-2,4-dione, dissolved in 20 ml of methylene chloride, are added dropwise. After 3 hours at 22° C., the reaction mixture is extracted by shaking with 2N hydrochloric acid. The separated methylene chloride phase is washed with water and then extracted by shaking with 10% aqueous sodium bicarbonate solution, dried over sodium sulfate and concentrated by evaporation. 3.18 g (100% of theory) of 2-methyl-6-trifluoromethyl-nicotinic acid 4-oxo-bicyclo[3.2.1]oct-2-en-2-yl ester are obtained in the form of an oil, which can be used further without purification.

Workup

  1. temperaturethe mixture is refluxed for 1 hour
  2. concentrationThe mixture is then concentrated
  3. customa rotary evaporator
  4. additionare added dropwise
  5. extractionthe reaction mixture is extracted
  6. washThe separated methylene chloride phase is washed with water
  7. extractionextracted
  8. stirringby shaking with 10% aqueous sodium bicarbonate solution
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-f6f11cdb6bcb4a28a581a3688dda6ded
Source dataset
uspto-grants-2005_05
Patent number
US06890885B2

Reaction notes

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