Dimethyl Sulfate → HCID 4337105, compound

Participants

Reaction Steps

To a suspension of 6-hydroxynaphthalene-2-sulfonic acid, sodium salt (5 g, 20.3 mmol) in 40 mL of 2:1 H2O/ethanol is added solid NaOH (0.89 g, 22.3 mmol) at room temperature. The resulting black mixture is stirred until a homogenous solution forms, and dimethyl sulfate (2.11 mL, 22.3 mmol) is then added. The mixture is stirred over a period of 16 hours as a precipitate eventually forms. The crude mixture is concentrated in vacuo and the residue is stirred in 70 mL of absolute EtOH as a slurry. The precipitate is filtered and dried. The solid is heated at reflux in 100 mL of 95% EtOH for 2.5 hours allowed to cool to room temperature, filtered and dried to give 3.31 g of crude 6-methoxynaphthalene-2-sulfonic acid, sodium salt. A mixture of the sulfonic acid, sodium salt (3.31 g, 12.7 mmol) in 5.3 mL of phosphorous oxychloride and phosphorous pentachloride (3.44 g, 16.5 mmol) is heated slowly to 60° C. until a homogenous solution forms and then is heated at 120° C. for 4 hours. The resulting mixture is allowed to stir at room temperature overnight, then is added slowly to a mixture of ice/ice water. The mixture is diluted with water and extracted with CHCl3. The combined organic layers are washed successively with water and saturated NaHCO3 solution. The organic phase is dried over anhydrous MgSO4, filtered and concentrated to give 4 g of a crude product. The crude product is purified by column chromatography in a gradient of 10% EtOAc/hexanes to 20% EtOAc/hexanes to afford the title compound (1.51 g, 5.88 mmol) as a crystalline solid.

Provenance & Evidence