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

HRID 1531639Notes

Reaction equation

HRID 1531639 reaction equation
Br[C:2]1[CH:7]=[C:6]([N:8]([CH3:10])[CH3:9])[CH:5]=[C:4]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[N:3]=1.C([Li])CCC.[C:27](=[O:29])=[O:28]>C(OCC)C>[CH3:9][N:8]([CH3:10])[C:6]1[CH:5]=[C:4]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[N:3]=[C:2]([C:27]([OH:29])=[O:28])[CH:7]=1

Participants

5

Reactant 3

HCID 280Carbon DioxideHCID 212498292-Bromo-N,N-dimethyl-6-[3-(trifluoromethyl)phenoxy]pyridin-4-amineHCID 178418339Butyllithium

Product 1

HCID 212498284-Dimethylamino-6-[3-(trifluoromethyl)phenoxy] picolinic acid

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

2-bromo-4-dimethylamino-6-[3-(trifluoromethyl)phenoxy] pyridine (5.00 g, 0.0138 mol) was dissolved in about 200 ml of diethyl ether. While cooling in a dry ice-acetone bath in an argon atmosphere, the obtained solution was mixed with n-butyl lithium [9.2 ml (ca. 1.66 M in hexane solution), 0.0138×1.1 mol], and then stirred for about 10 minutes. After the interior of the reactor was replaced with a carbon dioxide gas, the solution was removed from the bath and stirred at room temperature for about one hour. The reaction solution was mixed with about 15 ml of a 4 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. additionThe reaction solution was mixed with about 15 ml of a 4 N aqueous hydrochloric acid 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-583288195ada4096a3ca7843d7acfb95
Source dataset
uspto-grants-2001_03
Patent number
US06200933B1

Reaction notes

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