Dimethyl Sulfate → Methyl 3-bromo-2-methoxy-6-methylbenzoate

HRID 1778367Notes

Reaction equation

HRID 1778367 reaction equation
[Br:1][C:2]1[C:3]([OH:13])=[C:4]([C:9]([CH3:12])=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].S(OC)(O[CH3:18])(=O)=O.C(=O)([O-])[O-].[K+].[K+]>C1(S(CC2C(C(OC)=O)=C3C(C4C=COC=4CO3)=CC=2)(=O)=O)C=CC=CC=1>[Br:1][C:2]1[C:3]([O:13][CH3:18])=[C:4]([C:9]([CH3:12])=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 11430Potassium CarbonateHCID 66685369Methyl 3-bromo-2-hydroxy-6-methylbenzoate2×

Product 1

HCID 66685292Methyl 3-bromo-2-methoxy-6-methylbenzoate

Reagents, catalysts & solvents 1

HCID 66685555methyl 7-(benzenesulfonylmethyl)-4H-furo[2,3-c]chromene-6-carboxylateSolvent

Procedure

A mixture of methyl 3-bromo-2-hydroxy-6-methylbenzoate (Intermediate 44, 114.5 g), dimethyl sulfate (61 mL) and potassium carbonate (166 g) in acetone (11) was heated at reflux for 2.5 hours. After cooling, the mixture was filtered and the filtrate was evaporated to dryness. The residue was dissolved in DCM and washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of tert-butyl methyl ether and pentane with a gradient of 0-40%. The product was purified again by chromatography on silica, eluting with a mixture of tert-butyl methyl ether and pentane with a gradient of 0-10%. The product was again purified by chromatography on silica, eluting with a mixture of tert-butyl methyl ether and pentane with a gradient of 0-10% to give methyl 3-bromo-2-methoxy-6-methylbenzoate (66 g).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2.5 hours
  3. temperatureAfter cooling
  4. filtrationthe mixture was filtered
  5. customthe filtrate was evaporated to dryness
  6. dissolutionThe residue was dissolved in DCM
  7. washwashed with water
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customThe filtrate was evaporated to dryness
  11. customthe residue was purified by chromatography on silica
  12. washeluting with a mixture of tert-butyl methyl ether and pentane with a gradient of 0-40%
  13. customThe product was purified again by chromatography on silica
  14. washeluting with a mixture of tert-butyl methyl ether and pentane with a gradient of 0-10%
  15. customThe product was again purified by chromatography on silica
  16. washeluting with a mixture of tert-butyl methyl ether and pentane with a gradient of 0-10%

Sources & evidence

ORD record
ord-c712cf0b68ac444d868d42e229916df0
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

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