Sulfuric Acid → Methyl 4-(hydroxymethyl)-2-(trifluoromethyl)benzoate

HRID 467935Notes

Reaction equation

HRID 467935 reaction equation
[OH:1][CH2:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[C:5]([C:12]([F:15])([F:14])[F:13])[CH:4]=1.[C:16]1(C)C=CC=CC=1.S(=O)(=O)(O)O>CO>[CH3:16][O:8][C:7](=[O:9])[C:6]1[CH:10]=[CH:11][C:3]([CH2:2][OH:1])=[CH:4][C:5]=1[C:12]([F:13])([F:14])[F:15]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 1140TolueneHCID 110961264-(hydroxymethyl)-2-(trifluoromethyl)benzoic Acid

Product 1

HCID 57443316Methyl 4-(hydroxymethyl)-2-(trifluoromethyl)benzoate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-hydroxymethyl-2-trifluoromethyl-benzoic acid (Example I8) (9.07 g) in methanol (250 ml) was added toluene (250 ml) and concentrated sulfuric acid (4.5 ml). The reaction mixture was stirred at 80° C. for 16 hours. The methanol was removed and the residue diluted with aqueous sodium hydrogen carbonate (saturated) (150 ml) and ethyl acetate (150 ml). The phases were separated and the aqueous layer was extracted with more ethyl acetate (2×150 ml). The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated to give 4-hydroxymethyl-2-trifluoromethyl-benzoic acid methyl ester (5.97 g) as a colorless oil. 1H-NMR (CDCl3, 400 MHz): 8.76-7.27 (m, 3H), 4.78 (s, 2H), 3.93 (s, 3H), 2.5 (br s, 1H).

Workup

  1. customThe methanol was removed
  2. additionthe residue diluted with aqueous sodium hydrogen carbonate (saturated) (150 ml) and ethyl acetate (150 ml)
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted with more ethyl acetate (2×150 ml)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-22f562b031894f158d3d18db16e84b90
Source dataset
uspto-grants-2014_01
Patent number
US08623896B2

Reaction notes

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