p-Toluenesulfonic acid → HCID 10316741, compound

Participants

Reaction Conditions

Reaction Steps

Potassium hydroxide (0.22 g, 3.3 mM) is added to a 0° C. solution of 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzenepropanoic acid hydrazide (1.0 g, 3.4 mM) and carbon disulfide (0.22 mL, 7.2 mM) in methanol (36 mL). The reaction mixture is stirred at 0° C. for 2 hours then at room temperature for 4 hours. Iodomethane (0.21 mL, 3.4 mM) is added and stirring is continued overnight. The reaction is diluted with ether and washed twice with water, once with a saturated solution of sodium bicarbonate, and once with brine. Drying the organic phase over magnesium sulfate and evaporation gives 1.2 g of crude intermediate which is dissolved in toluene (20 mL). p-Toluenesulfonic acid (0.72 g, 3.8 mM) is added to the solution and the reaction is heated at reflux for 1.5 hours. The reaction solution is cooled and filtered. The filtrate is diluted with ether and washed twice with water, once with a saturated solution of sodium bicarbonate, and once with brine. Drying the organic phase over magnesium sulfate and evaporation gives a crude product which is chromatographed on silica gel eluting with 1:9 then 2:8 ethyl acetate:hexane yielding 0.29 g (25%) of a white solid which is 2,6-bis(1,1-dimethylethyl)-4-[2-[5-(methylthio)-1,3,4-thiadiazol-2-yl]ethyl]phenol; mp 135°-139° C.

Provenance & Evidence