Hydrochloric Acid → 2,2-bis(fluoromethyl)-6-trifluoromethyl-2H-1-benzopyran-4-carboxylic acid

HRID 397021Notes

Reaction equation

HRID 397021 reaction equation
[C]=O.[F:3][CH2:4][C:5]1([CH2:27][F:28])[CH:10]=[C:9](OS(C(F)(F)F)(=O)=O)[C:8]2[CH:19]=[C:20]([C:23]([F:26])([F:25])[F:24])[CH:21]=[CH:22][C:7]=2[O:6]1.[C:29]([O-:32])(=[O:31])C.[K+].[Cl-].[Li+].[OH-].[Na+].Cl>CN(C)C=O>[F:3][CH2:4][C:5]1([CH2:27][F:28])[CH:10]=[C:9]([C:29]([OH:32])=[O:31])[C:8]2[CH:19]=[C:20]([C:23]([F:24])([F:25])[F:26])[CH:21]=[CH:22][C:7]=2[O:6]1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 433294Lithium ChlorideHCID 517044Potassium AcetateHCID 12070531trifluoromethanesulfonic acid 2,2-bis(fluoromethyl)-6-(trifluoromethyl)-2H-1-benzopyran-4-yl esterHCID 178418416HCID 178418416, compound2×

Product 1

HCID 98796402,2-bis(fluoromethyl)-6-trifluoromethyl-2H-1-benzopyran-4-carboxylic acidYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A three-necked 50-ml flask (equipped with a reflux condenser, a thermometer, and a CO introducing pipe connected with a balloon charged with carbon monoxide gas) was charged with 2.00 g (4.85 mmol) of trifluoromethanesulfonic acid 2,2-bis(fluoromethyl)-6- (trifluoromethyl)-2 H-1-benzopyran-4-yl ester, 1.90 g (19.4 mmol) of potassium acetate, 206 mg (4.85 mmol) of lithium chloride, and 25 ml of N,N-dimethylformamide. Under stirring of the mixture, 50 mg (0.0485 mmol) of tris(dibenzylidene)(chloroform)dipalladium (Pd2(dba)3(CHCl3)) were added. Under normal pressure, the reaction was conducted at 25° C. for 2 hr, while maintaining carbon monoxide atmosphere. After the reaction, the reaction liquid was poured into 50 ml of 2 mol/L sodium hydroxide aqueous solution, followed by shaking for 20 min, then adding concentrated hydrochloric acid to make it acid, and then extraction two times with 50 ml of MTBE. The resulting two MTBE extracts were combined together, followed by washing with water, then by drying with 5 g of magnesium sulfate anhydride, and then by filtration. Then, the MTBE was distilled off by an evaporator. The resulting residue was dissolved in 50 ml of a saturated sodium hydrogencarbonate aqueous solution, followed by washing with 5 ml of methylene chloride. The resulting aqueous layer was made acid by concentrated hydrochloric acid, followed by extraction two times with 50 ml of MTBE. The resulting two MTBE extracts were combined together, followed by washing with water, then by drying with 5 g of magnesium sulfate anhydride, and then by filtration. Then, the MTBE was distilled off by an evaporator, thereby obtaining 1.30 g (4.22 mmol) of 2,2-bis(fluoromethyl)-6-(trifluoromethyl)-2 H-1- benzopyran- 4-carboxylic acid (yield: 87.0%).

Workup

  1. customA three-necked 50-ml flask (equipped with a reflux condenser
  2. additionwere added
  3. customAfter the reaction
  4. customthe reaction liquid
  5. extractionextraction two times with 50 ml of MTBE
  6. washby washing with water
  7. dry with materialby drying with 5 g of magnesium sulfate anhydride
  8. filtrationby filtration
  9. distillationThen, the MTBE was distilled off by an evaporator
  10. dissolutionThe resulting residue was dissolved in 50 ml of a saturated sodium hydrogencarbonate aqueous solution
  11. washby washing with 5 ml of methylene chloride
  12. extractionfollowed by extraction two times with 50 ml of MTBE
  13. washby washing with water
  14. dry with materialby drying with 5 g of magnesium sulfate anhydride
  15. filtrationby filtration
  16. distillationThen, the MTBE was distilled off by an evaporator

Sources & evidence

ORD record
ord-bab51bbc87494920a990e9c3e8347868
Source dataset
uspto-grants-2003_08
Patent number
US06608217B2

Reaction notes

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