Sodium Hydroxide → 4-Fluoro-3,5-diisopropoxybenzoic acid

HRID 62774Notes

Reaction equation

HRID 62774 reaction equation
CC1(C)N([O])C(C)(C)CCC1.[F:12][C:13]1[C:18]([O:19][CH:20]([CH3:22])[CH3:21])=[CH:17][C:16]([CH2:23][OH:24])=[CH:15][C:14]=1[O:25][CH:26]([CH3:28])[CH3:27].Cl([O-])=[O:30].[Na+].Cl[O-].[Na+].[OH-].[Na+].S([O-])([O-])=O.[Na+].[Na+]>CC#N.P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+].O>[F:12][C:13]1[C:18]([O:19][CH:20]([CH3:22])[CH3:21])=[CH:17][C:16]([C:23]([OH:30])=[O:24])=[CH:15][C:14]=1[O:25][CH:26]([CH3:28])[CH3:27]

Participants

10

Reactant 6

HCID 14798Sodium HydroxideHCID 24437Sodium SulfiteHCID 2724126TempoHCID 23665760Sodium HypochloriteHCID 23668197Sodium ChloriteHCID 67041705(4-Fluoro-3,5-diisopropoxyphenyl)methanol

Product 1

HCID 670418744-Fluoro-3,5-diisopropoxybenzoic acidYield 12.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 24243Trisodium PhosphateSolvent

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−).

Workup

  1. additionthe other every 10 min until the addition
  2. washthe aqueous mixture was washed with diethyl ether (50 mL)
  3. additionThe aqueous layer was acidified by the addition of 4M HCl
  4. extractionthe product was extracted into EtOAc (50 mL)
  5. dry with materialThe organic solution was dried over MgSO4
  6. filtrationfiltered
  7. customthe solvent was removed in vacuo
  8. customThe residue was purified by silica gel chromatography (12 g, 0-40% EtOAc in isohexane)

Sources & evidence

ORD record
ord-658b9ad515dc49beb866f314d73454bc
Source dataset
uspto-grants-2016_09
Patent number
US09447028B2

Reaction notes

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