Reaction #91052

Reaction equation

Sodium chlorite

sodium hypochlorite

NaOH

TEMPO

(4-fluoro-3,5-diisopropoxyphenyl)methanol

(4-Fluoro-3,5-diisopropoxyphenyl)methanol

Sodium sulfite

→

4-fluoro-3,5-diisopropoxybenzoic acid

Yield 12.3%

4-Fluoro-3,5-diisopropoxybenzoic acid

Yield 12.3%

Solvents

water

MeCN

sodium phosphate

Conditions

Workup

1. 1
   workup.ADDITIONthe other every 10 min until the addition
2. 2
   Washthe aqueous mixture was washed with diethyl ether (50 mL)
3. 3
   workup.ADDITIONThe aqueous layer was acidified by the addition of 4M HCl
4. 4
   Extractionthe product was extracted into EtOAc (50 mL)
5. 5
   DryingThe organic solution was dried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Otherthe solvent was removed in vacuo
8. 8
   OtherThe residue was purified by silica gel chromatography (12 g, 0-40% EtOAc in isohexane)

Procedure

TEMPO (12 mg, 79 μmol) was added to (4-fluoro-3,5-diisopropoxyphenyl)methanol (7) (382 mg, 1.58 mmol) in a mixture of MeCN (10 mL) and sodium phosphate buffer at 35° C. Sodium chlorite (285 mg, 3.15 mmol) in water (5 mL) and sodium hypochlorite (97 μl, 1.6 mmol) were added cautiously (portionwise, 20% of one then the other every 10 min until the addition was complete). Once the reaction was complete the mixture was basified to pH 9 by the addition of NaOH (15 mL). Sodium sulfite (aq., 20 mL) was added and the aqueous mixture was washed with diethyl ether (50 mL). The aqueous layer was acidified by the addition of 4M HCl and the product was extracted into EtOAc (50 mL). The organic solution was dried over MgSO4, filtered and the solvent was removed in vacuo. The residue was purified by silica gel chromatography (12 g, 0-40% EtOAc in isohexane) to afford 4-fluoro-3,5-diisopropoxybenzoic acid (8) (50 mg, 12%) as a white solid: m/z 255 [M−H]− (ES−).

Source