Hydrochloric Acid → 4,5-Dichloro-2-(4-fluoro-2-methoxyphenoxy)benzoic acid

HRID 515088Notes

Reaction equation

HRID 515088 reaction equation
[Cl:1][C:2]1[C:9]([Cl:10])=[CH:8][C:5]([CH:6]=[O:7])=[C:4]([O:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=2[O:19][CH3:20])[CH:3]=1.P([O-])(O)(O)=[O:22].[Na+].CC(=CC)C.Cl([O-])=O.[Na+].Cl.S([O-])([O-])=O.[Na+].[Na+]>CC(O)(C)C.O.C(#N)C.C(OCC)(=O)C>[Cl:1][C:2]1[C:9]([Cl:10])=[CH:8][C:5]([C:6]([OH:22])=[O:7])=[C:4]([O:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=2[O:19][CH3:20])[CH:3]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 105532-Methyl-2-buteneHCID 24437Sodium SulfiteHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 903146634,5-Dichloro-2-(4-fluoro-2-methoxy-phenoxy)benzaldehyde

Product 1

HCID 903143794,5-Dichloro-2-(4-fluoro-2-methoxyphenoxy)benzoic acidYield 85%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 4,5-dichloro-2-(4-fluoro-2-methoxy-phenoxy)benzaldehyde (3.3 g, 10.47 mmol) in tBuOH (33.00 mL), water (19.80 mL) and acetonitrile (19.80 mL) was added sodium dihydrogen phosphate (655.9 μL, 10.47 mmol), 2-methylbut-2-ene (5.54 mL, 52.35 mmol) and sodium chlorite (2.84 g, 31.41 mmol). The reaction mixture was stirred at 25° C. for 1 h. The reaction mixture was acidified with 1N HCl and diluted with ethyl acetate. Sodium sulfite was added to remove the faint yellow color. The two layers were separated and the aqueous layer was extracted with ethyl acetate (3×25 mL). The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated. The solid was triturated with hexanes and filtered to provide 4,5-dichloro-2-(4-fluoro-2-methoxy-phenoxy)benzoic acid (2.94 g, 85%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 13.37 (br s, 1H), 7.96 (s, 1H), 7.18-7.12 (m, 2H), 6.86-6.80 (m, 2H), 3.76 (s, 3H) ppm.

Workup

  1. customto remove the faint yellow color
  2. customThe two layers were separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (3×25 mL)
  4. washThe combined organics were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe solid was triturated with hexanes
  9. filtrationfiltered

Sources & evidence

ORD record
ord-44ed805addf44ea795ce0b6bf4d3c058
Source dataset
uspto-grants-2015_08
Patent number
US09108903B2

Reaction notes

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