Hydrochloric Acid → 2-(2-Chloro-4-fluoro-phenoxy)-6-(trifluoromethyl)benzoic acid

HRID 1484174Notes

Reaction equation

HRID 1484174 reaction equation
[Cl:1][C:2]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[C:6]=1[CH:7]=[O:8].CC(=CC)C.P([O-])(O)(O)=[O:28].[Na+].Cl([O-])=O.[Na+].Cl>CC(O)(C)C.O.CC#N>[Cl:1][C:2]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[C:6]=1[C:7]([OH:28])=[O:8]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 903145132-(2-Chloro-4-fluoro-phenoxy)-6-(trifluoromethyl)benzaldehyde

Product 1

HCID 903153352-(2-Chloro-4-fluoro-phenoxy)-6-(trifluoromethyl)benzoic acidYield 122.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(2-chloro-4-fluoro-phenoxy)-6-(trifluoromethyl)benzaldehyde (31 g, 97.29 mmol) in tBuOH (155.0 mL), water (100.8 mL), CH3CN (155.0 mL) and 2-methyl-2-butene (51.45 mL, 486.4 mmol) was added sodium dihydrogen phosphate (35.02 g, 291.9 mmol) and the mixture was cooled to 0° C. Sodium chlorite (26.40 g, 291.9 mmol) was added in one portion and the mixture was stirred at 25° C. for 1 hour. The pH of the reaction was adjusted to 2-3 with 1N HCl and the layers were separated. The aqueous layer was extracted with EtOAc (3×). All the organic layers were combined, and solid sodium sulfite (˜5 g) was added followed by brine (50 ml) and 1N NaOH (10 ml) and the mixture was shaken until the yellow color disappeared. The layers were separated and the organic was washed with brine, dried over Na2SO4, filtered through a short plug of silica and evaporated to dryness to give 2-(2-chloro-4-fluoro-phenoxy)-6-(trifluoromethyl)benzoic acid (40 g, 98%) as an oil that was used in the next step without further purification. ESI-MS m/z calc. 334.00. found 335.1 (M+1)+; Retention time: 1.58 minutes (3 minutes run).

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted with EtOAc (3×)
  3. additionsolid sodium sulfite (˜5 g) was added
  4. stirringthe mixture was shaken until the yellow color
  5. customThe layers were separated
  6. washthe organic was washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered through a short plug of silica
  9. customevaporated to dryness

Sources & evidence

ORD record
ord-1faa718bf56e447da0c286380e753487
Source dataset
uspto-grants-2016_08
Patent number
US09421196B2

Reaction notes

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