Dimethyl Sulfate → HCID 18950856, compound

HRID 1492756Notes

Reaction equation

HRID 1492756 reaction equation
Br[CH2:2][C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[C:5]#[N:6].[OH:11][C:12]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][C:13]=1[C:14]([O:16][CH3:17])=O.[H-].[Na+].S(OC)(OC)(=O)=O>C1COCC1>[CH3:17][O:16][C:14]1[C:13]2[CH:18]=[C:19]([CH3:22])[CH:20]=[CH:21][C:12]=2[O:11][C:2]=1[C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[C:5]#[N:6]

Participants

6

Reactant 4

HCID 6497Dimethyl SulfateHCID 24758Sodium hydride3×HCID 895992-(Bromomethyl)benzonitrileHCID 89802Methyl 5-methylsalicylate

Product 1

HCID 18950856HCID 18950856, compoundYield 71.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(Bromomethyl)benzonitrile (17.6 g) was added to a mixture of methyl 2-hydroxy-5-methylbenzoate (15 g) and sodium hydride (2.7 g, 80% dispersion in oil) in dry THF (150 ml) and the resulting mixture heated at reflux for 5 h. Further sodium hydride (2.7 g, 80% dispersion in oil) was added and heating continued overnight. The mixture was cooled (0° C.), sodium hydride (2.7 g, 80% dispersion in oil) and dimethyl sulphate (17 ml) were added, and the resulting solution stirred at room temperature for 4 h. Solvent was removed in vacuo, the residue taken up in dichloromethane (200 ml) and cone. ammonia solution (200 ml) added carefully. The organic solution was removed and the aqueous solution extracted with dichloromethane (2×200 ml). The combined, dried organic phases were evaporated in vacuo and the residue purified by chromatography, eluting with dichloromethane: hexane (1:1) to give the title compound as a white solid (17 g).

Workup

  1. temperaturethe resulting mixture heated
  2. temperatureat reflux for 5 h
  3. temperatureheating continued overnight
  4. additionwere added
  5. customSolvent was removed in vacuo
  6. additionammonia solution (200 ml) added carefully
  7. customThe organic solution was removed
  8. extractionthe aqueous solution extracted with dichloromethane (2×200 ml)
  9. customdried organic phases were evaporated in vacuo
  10. customthe residue purified by chromatography
  11. washeluting with dichloromethane: hexane (1:1)

Sources & evidence

ORD record
ord-a11ddc6224e2428f90da6bee50456647
Source dataset
uspto-grants-1994_12
Patent number
US05374646

Reaction notes

Loading…