Methanol → Methyl 4-(Chlorosulfonyl)benzoate

HRID 737004Notes

Reaction equation

HRID 737004 reaction equation
[Cl:1][S:2]([C:5]1[CH:13]=[CH:12][C:8]([C:9](Cl)=[O:10])=[CH:7][CH:6]=1)(=[O:4])=[O:3].C(N(CC)CC)C.[CH3:21][OH:22]>C1COCC1.CN(C1C=CN=CC=1)C.CCOC(C)=O.Cl>[CH3:21][O:22][C:9](=[O:10])[C:8]1[CH:12]=[CH:13][C:5]([S:2]([Cl:1])(=[O:4])=[O:3])=[CH:6][CH:7]=1

Participants

8

Reactant 3

HCID 887MethanolHCID 8471TriethylamineHCID 820244-(Chlorosulphonyl)benzoyl chloride

Product 1

HCID 4738388Methyl 4-(Chlorosulfonyl)benzoateYield 93.1%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

In a 22 L RBF, charge 4-Chlorosulfonyl-benzoyl chloride (990 g, 4.159 mole) in 8.3 L THF and cool to −78° C. In an addition funnel charge triethylamine (588 ml, 4.159 mole), methanol (168 ml, 4.159 mole), DMAP (5 g, 0.041 mole) and 4 L THF; add this solution dropwise to the reaction keeping the exotherm <−70° C. over 5 hours. After the addition is complete, stir the reaction in a cold bath overnight. Filter the reaction and rinse with 3×500 ml THF. Concentrate under vacuum the filtrate to give a yellow solid. Dissolve the solid in 7 L EtOAc and 7 L 1N HCl. Separate the organic layer and wash with 5 L brine. Dry the organics over Na2SO4, filter and concentrate under vacuum to give a white solid, 4-Chlorosulfonyl-benzoic acid methyl ester. Yield=93.1% (906 g).

Workup

  1. additionadd this solution dropwise to the reaction
  2. customthe exotherm <−70° C.
  3. customover 5 hours
  4. additionAfter the addition
  5. customthe reaction in a cold bath overnight
  6. filtrationFilter
  7. customthe reaction
  8. washrinse with 3×500 ml THF
  9. concentrationConcentrate under vacuum the filtrate
  10. customto give a yellow solid
  11. customSeparate the organic layer
  12. washwash with 5 L brine
  13. dry with materialDry the organics over Na2SO4
  14. filtrationfilter
  15. concentrationconcentrate under vacuum

Sources & evidence

ORD record
ord-0b1bd8ac24ba46f4b0800b0288e6b5c5
Source dataset
uspto-grants-2009_09
Patent number
US07595339B2

Reaction notes

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