Methyl iodide → Methyl 5-bromo-2-(methylthio)benzoate

HRID 337621Notes

Reaction equation

HRID 337621 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[Br:7][C:8]1[CH:9]=[CH:10][C:11]([SH:17])=C([CH:16]=1)C(O)=O.I[CH3:19].[H-].[Na+].[NH4+].[Cl-].C[CH2:25][O:26][C:27]([CH3:29])=[O:28]>CN(C=O)C>[Br:7][C:8]1[CH:9]=[CH:10][C:11]([S:17][CH3:19])=[C:29]([CH:16]=1)[C:27]([O:26][CH3:25])=[O:28]

Participants

8

Reactant 6

HCID 6328Methyl iodide2×HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 123255215-Bromo-2-mercaptobenzoic acid

Product 1

HCID 26966744Methyl 5-bromo-2-(methylthio)benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a DMF (0.2 M) suspension of cesium carbonate (3 eq.) and 5-bromo-2-mercaptobenzoic acid (1 eq.) was added iodomethane (5 eq.). The resulting suspension was then stirred at RT for 1 h. The volatiles were removed before EtOAc and sat. aq. NH4Cl were added. The organic phase was separated, dried over Na2SO4, filtered and the filtrate concentrated in vacuo to a pale yellow oil. This was taken up again in DMF (0.2 M) and added sequentially sodium hydride (3 eq.) and iodomethane (5 eq.). The reaction vessel was then sealed and heated to 70° C. for 16 h. After cooling to RT, EtOAc and sat. aq. NH4Cl were added to the crude reaction mixture. The organic phase was separated, dried over MgSO4, filtered and the filtrate concentrated in vacuo to a brown oil. Purification of the crude product thus obtained by way of flash chromatography (SiO2, Hex→3:2 (v/v) Hex:EtOAc) afforded the title compound as a light yellow solid.

Workup

  1. customThe volatiles were removed before EtOAc and sat. aq. NH4Cl
  2. additionwere added
  3. customThe organic phase was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated in vacuo to a pale yellow oil
  7. customThe reaction vessel was then sealed
  8. temperatureheated to 70° C. for 16 h
  9. temperatureAfter cooling to RT
  10. customreaction mixture
  11. customThe organic phase was separated
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationthe filtrate concentrated in vacuo to a brown oil
  15. customPurification of the crude product
  16. customthus obtained by way of flash chromatography (SiO2, Hex→3:2 (v/v) Hex:EtOAc)

Sources & evidence

ORD record
ord-434203c1f2814b2c85c91bf6ffe27a77
Source dataset
uspto-grants-2014_11
Patent number
US08889714B2

Reaction notes

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