Carbon Dioxide → 2-Methoxy-4,6-bis(trifluoromethyl)benzoic acid

HRID 2167361Notes

Reaction equation

HRID 2167361 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[C:5]([C:13]([F:16])([F:15])[F:14])[CH:4]=1.[Li]CCCC.[C:22](=[O:24])=[O:23]>CCOCC>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]([F:14])([F:15])[F:16])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[C:8]=1[C:22]([OH:24])=[O:23]

Participants

5

Reactant 3

HCID 280Carbon DioxideHCID 27378043,5-Bis(trifluoromethyl)anisoleHCID 178418339Butyllithium

Product 1

HCID 27412872-Methoxy-4,6-bis(trifluoromethyl)benzoic acidYield 50%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of 1-methoxy-3,5-bis(trifluoromethyl)benzene (48, 0.56 g, 2.33 mmol) in anhydrous ether (5 mL) was slowly added n-BuLi (1.6 M solution in hexanes, 3 mL, 4.66 mmol) at 0° C. The reaction mixture was stirred at room temperature for 1 h. Dry ice was added into the yellow suspension until the starting material was completely consumed as monitored by TLC. The reaction was quenched with H2O (3 mL) and organic layer was separated. The aqueous layer was acidified with concentrated HCl, and then extracted with Et2O (3×5 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to afford 2-methoxy-4,6-bis(trifluoromethyl)benzoic acid (49, 0.38 g, 50%): 1H NMR (300 MHz, DMSO-d6) δ 13.94 (s, 1H), 7.76 (s, 1H), 3.97 (s, 1H).

Workup

  1. customat 0° C
  2. customwas completely consumed
  3. customThe reaction was quenched with H2O (3 mL) and organic layer
  4. customwas separated
  5. extractionextracted with Et2O (3×5 mL)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4bcdc57eaf5342baa3df2a8ce477f266
Source dataset
uspto-grants-2015_06
Patent number
US09045445B2

Reaction notes

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