Potassium Carbonate → Methyl 2-fluoro-6-hydroxy-4-(methylsulfonyl)benzoate

HRID 452466Notes

Reaction equation

HRID 452466 reaction equation
Br[C:2]1[CH:11]=[C:10]([OH:12])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([F:13])[CH:3]=1.[CH3:14][S:15]([O-:17])=[O:16].[Na+].N1CCC[C@H]1C(O)=O.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.[Cu]I>[F:13][C:4]1[CH:3]=[C:2]([S:15]([CH3:14])(=[O:17])=[O:16])[CH:11]=[C:10]([OH:12])[C:5]=1[C:6]([O:8][CH3:9])=[O:7]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 2733271Sodium methanesulfinateHCID 66886502Methyl 4-bromo-2-fluoro-6-hydroxybenzoate

Product 1

HCID 66887484Methyl 2-fluoro-6-hydroxy-4-(methylsulfonyl)benzoateYield 10.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
95 °C

Procedure

Methyl 4-bromo-2-fluoro-6-hydroxybenzoate (1.7 g, 5.6 mmol), sodium methanesulfinate (95%) (0.91 g, 8.5 mmol), CuI (0.64 g, 3.4 mmol), L-proline (0.78 g, 6.8 mmol) and K2CO3 (0.47 g, 3.4 mmol) was dissolved in DMSO (dry) (10 ml). Nitrogen was bubbled through the solution for 15 min. The mixture was stirred and heated at 95° C. for 6 h under nitrogen. After cooling to RT, the mixture was filtered on a plug of silica and eluted with ETOAc. The filtrate was washed with 1M citric acid. The waterlayer was extracted once with EtOAc. The combined organic phases were washed with brine, dried (Na2SO4), filtered and concentrated. Purification on flash column chromatography (isooctane/EtOAc) gave the crude title compound (0.14 g). MS m/z (rel. intensity, 70 eV) 248 (M+, 36), 216 (bp), 173 (19), 125 (20), 81 (24).

Workup

  1. customNitrogen was bubbled through the solution for 15 min
  2. temperatureAfter cooling to RT
  3. filtrationthe mixture was filtered on a plug of silica
  4. washeluted with ETOAc
  5. washThe filtrate was washed with 1M citric acid
  6. extractionThe waterlayer was extracted once with EtOAc
  7. washThe combined organic phases were washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification on flash column chromatography (isooctane/EtOAc)

Sources & evidence

ORD record
ord-72180e4894a74bbeb598f96ca12253a8
Source dataset
uspto-grants-2013_07
Patent number
US08492372B2

Reaction notes

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