Sodium Hydroxide → Methyl 3-chloro-5-(methylsulfonyl)benzoate

HRID 403403Notes

Reaction equation

HRID 403403 reaction equation
N1CCC[C@H]1C(O)=O.[OH-].[Na+].[CH3:11][O:12][C:13](=[O:22])[C:14]1[CH:19]=[C:18](I)[CH:17]=[C:16]([Cl:21])[CH:15]=1.[CH3:23][S:24]([O-:26])=[O:25].[Na+].C(=O)(O)[O-].[Na+]>CS(C)=O.[Cu]I.C(OCC)(=O)C>[CH3:11][O:12][C:13](=[O:22])[C:14]1[CH:19]=[C:18]([S:24]([CH3:23])(=[O:26])=[O:25])[CH:17]=[C:16]([Cl:21])[CH:15]=1

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 145742L-ProlineHCID 516892Sodium BicarbonateHCID 2733271Sodium methanesulfinateHCID 24721134Methyl 3-chloro-5-iodobenzoate

Product 1

HCID 18952494Methyl 3-chloro-5-(methylsulfonyl)benzoateYield 55.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of L-proline (1.553 g, 13.49 mmol, CAS RN 147-85-3) in dimethylsulfoxide (80 mL) was added sodium hydroxide (0.54 g, 13.49 mmol) and the reaction mixture was stirred at 25° C. for 30 min. Then copper(I) iodide (2.568 g, 13.49 mmol), 3-chloro-5-iodo-benzoic acid methyl ester (5.0 g, 16.86 mmol, CAS RN 289039-85-6) and sodium methanesulfinate (13.77 g, 134.9 mmol, CAS RN 20277-69-4) were added to the reaction mixture and the reaction mixture was heated at 120° C. for 2 h. The reaction mixture was allowed to cool down, poured on saturated aqueous sodium bicarbonate solution (500 mL) and ethyl acetate (500 mL) and filtered through celite. The organic layer was separated and the aqueous layer was extracted twice with ethyl acetate (200 mL each). The combined organic layers were washed with cold water (200 mL) and brine (100 mL), dried over anhydrous sodium sulfate and evaporated. The residue was purified by column chromatography over silica gel (100-200 mesh) with a gradient of ethyl acetate:n-hexane (1:10 to 2:10) to get the desired compound as a colorless solid (2.31 g, 55%). MS (EI): m/z=248 ([M]).

Workup

  1. temperaturethe reaction mixture was heated at 120° C. for 2 h
  2. temperatureto cool down
  3. filtrationfiltered through celite
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted twice with ethyl acetate (200 mL each)
  6. washThe combined organic layers were washed with cold water (200 mL) and brine (100 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. customevaporated
  9. customThe residue was purified by column chromatography over silica gel (100-200 mesh) with a gradient of ethyl acetate:n-hexane (1:10 to 2:10)

Sources & evidence

ORD record
ord-a6c1238f57a64e06b96eec7655f9a8db
Source dataset
uspto-grants-2014_06
Patent number
US08748434B2

Reaction notes

Loading…