Carbon Dioxide → 4-Methoxy-6-[3-(trifluoromethyl)phenoxy] picolinic acid

HRID 1531633Notes

Reaction equation

HRID 1531633 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[N:3]=1.C([Li])CCC.[C:26](=[O:28])=[O:27].Cl>C(OCC)C.C(OCC)(=O)C.O>[CH3:9][O:8][C:6]1[CH:5]=[C:4]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[N:3]=[C:2]([C:26]([OH:28])=[O:27])[CH:7]=1

Participants

7

Reactant 4

HCID 280Carbon DioxideHCID 313Hydrochloric AcidHCID 111318162-Bromo-4-methoxy-6-[3-(trifluoromethyl)phenoxy] pyridineHCID 178418339Butyllithium

Product 1

HCID 109030764-Methoxy-6-[3-(trifluoromethyl)phenoxy] picolinic acid

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 22728543Water ethylacetateSolvent

Procedure

2-bromo-4-methoxy-6-[3-(trifluoromethyl)phenoxy] pyridine (3.00 g, 0.0086 mol) was suspended in about 30 ml of diethyl ether. While cooling in a dry ice-acetone bath in an argon atmosphere, the obtained suspension was mixed with n-butyl lithium [5.9 ml (ca. 1.6 M in hexane solution), 0.0086×1.1 mol], and the obtained mixture was stirred for about 10 minutes. After replacing an interior of the reactor with a carbon dioxide gas, the solution was removed from the bath and stirred at room temperature for about one hour. The obtained reaction solution was mixed with about 10 ml of a 1 N aqueous hydrochloric acid solution, distributed in ethyl acetate-water, and then washed with saturated brine. The organic phase separated from the solution was dried with anhydrous sodium sulfate, concentrated and then purified by silica gel column chromatography (eluting solution: ethyl acetate/hexane), thereby obtaining an aimed product.

Workup

  1. temperatureWhile cooling in a dry ice-acetone bath in an argon atmosphere
  2. customthe solution was removed from the bath
  3. stirringstirred at room temperature for about one hour
  4. customThe obtained reaction solution
  5. washwashed with saturated brine
  6. customThe organic phase separated from the solution
  7. dry with materialwas dried with anhydrous sodium sulfate
  8. concentrationconcentrated
  9. custompurified by silica gel column chromatography (eluting solution: ethyl acetate/hexane)

Sources & evidence

ORD record
ord-b0c094c9c65c4cebb03fbf29d601c3d2
Source dataset
uspto-grants-2001_03
Patent number
US06200933B1

Reaction notes

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