4-Hydroxy-3-methoxy-5-(trifluoromethyl)benzaldehyde → 4-Hydroxy-3-methoxy-5-(trifluoromethyl)benzoic acid

HRID 62778Notes

Reaction equation

HRID 62778 reaction equation
[OH:1][C:2]1[C:9]([C:10]([F:13])([F:12])[F:11])=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[O:14][CH3:15].[OH:16]OS([O-])=O.[K+]>CN(C=O)C.CCOC(C)=O>[OH:1][C:2]1[C:9]([C:10]([F:12])([F:13])[F:11])=[CH:8][C:5]([C:6]([OH:16])=[O:7])=[CH:4][C:3]=1[O:14][CH3:15]

Participants

5

Reactant 2

HCID 193891994-Hydroxy-3-methoxy-5-(trifluoromethyl)benzaldehydeHCID 23707502Potassium hydroxy sulfite

Product 1

HCID 670417934-Hydroxy-3-methoxy-5-(trifluoromethyl)benzoic acidYield 35%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 4-hydroxy-3-methoxy-5-(trifluoromethyl)benzaldehyde (1.03 g, 4.68 mmol) and Oxone™ (3.45 g, 5.61 mmol) in DMF (10 mL) was stirred at RT for 2 h. The reaction mixture was diluted with EtOAc (40 mL) and the solution was washed sequentially with 1M HCl (40 mL) and brine (4×40 mL). The solvent was removed in vacuo and the residue was purified by silica gel chromatography (80 g, 0-10% MeOH in DCM) to afford 4-hydroxy-3-methoxy-5-(trifluoromethyl)benzoic acid (4) (392 mg, 35%) as a white solid: m/z 235 [M−H]− (ES−); 1H NMR (400 MHz, DMSO-d6) δ: 13.01 (1H, br s), 10.74 (1H, br s), 7.68 (2H, dd), 3.92 (3H, s).

Workup

  1. washthe solution was washed sequentially with 1M HCl (40 mL) and brine (4×40 mL)
  2. customThe solvent was removed in vacuo
  3. customthe residue was purified by silica gel chromatography (80 g, 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-20d065d849854b009167d7b80c890b4d
Source dataset
uspto-grants-2016_09
Patent number
US09447028B2

Reaction notes

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