Formic Acid → 4-Fluoro-alpha-[[(2-fluorophenyl)thio]methyl]benzeneacetic acid

HRID 22193

Reaction equation

HRID 22193 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:14][S:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[F:22])[C:9]([O:11]CC)=[O:10])=[CH:4][CH:3]=1.C(O)=O.CS(O)(=O)=O.O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([CH2:14][S:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[F:22])[C:9]([OH:11])=[O:10])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 284Formic AcidHCID 962WaterHCID 6395Methanesulfonic AcidHCID 19927552Ethyl 4-fluoro-alpha-[[(2-fluorophenyl)thio]methyl]benzeneacetate

Product 1

HCID 199275564-Fluoro-alpha-[[(2-fluorophenyl)thio]methyl]benzeneacetic acidYield 95.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The crude ester from Step B (5.3 g, 16 mmole) was combined with 20 ml of 88% formic acid and 2.1 ml (33 mmole) of methane sulfonic acid. The emulsion was refluxed for five hours during which time it gradually became homogeneous. After cooling, water and methylene chloride were added and the aqueous phase was separated and extracted twice with methylene chloride. The organic phases were combined, dried (MgSO4) and concentrated. The crude residue was taken up in 4% ethyl acetate/hexane and filtered through a plug of silica gel to remove nonpolar impurities. The product acid was then rinsed from the silica gel with ethyl acetate and the solvent concentrated. The acid was a colorless solid (4.5 g, 95% yield). 1H NMR (CDCl3) δ: 10.05 (1H, br s), 7.20 (5H, m), 7.03 (3H, m), 3.81 (1H, dd, J=6, 8 Hz), 3.57 (1H, m), 3.23 (1H, dd, J= 6, 12 Hz).

Workup

  1. temperatureThe emulsion was refluxed for five hours during which time it gradually became homogeneous
  2. temperatureAfter cooling
  3. customthe aqueous phase was separated
  4. extractionextracted twice with methylene chloride
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. filtrationfiltered through a plug of silica gel
  8. customto remove nonpolar impurities
  9. washThe product acid was then rinsed from the silica gel with ethyl acetate
  10. concentrationthe solvent concentrated

Sources & evidence

ORD record
ord-8483dd164cf14465bb793c280b8948c3
Source dataset
uspto-grants-1995_06
Patent number
US05428027

Linked notes

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