Diethyl Malonate → Diethyl 2-(methylthio)benzyl-malonate

Participants

Reaction Steps

By reacting thiosalicylic acid with dimethyl sulfate in the presence of tetrabutylammonium bromide, there was obtained methyl 2-(methylthio)benzoate, melting point 64° C. Reduction with lithium aluminum hydride in dry tetrahydrofuran yielded 2-(methylthio)benzyl alcohol which was converted by reaction with SOCl2 into 2-(methylthio)benzyl chloride, boiling point 90° C./0.3 Torr. Reaction of diethyl malonate with 2-(methylthio)benzyl chloride yielded diethyl 2-(methylthio)benzyl-malonate, boiling point 130° C./0.05 Torr. Condensation with formamidine yielded 5-[o-(methylthio)benzyl]-6-hydroxy-4(3H)-pyrimidinone which was converted into 4,6-dichloro-5-[o-(methylthio)benzyl]pyrimidine, melting point 91° C. From 4,6-dichloro-5-(o-(methylthio)benzyl)pyrimidine and p-isopropylbenzenesulfonamide potassium, there was finally obtained N-[6-chloro-5-(o-(methylthio)benzyl)-4-pyrimidinyl]-p-isopropylbenzenesulfonamide, melting point 145°-146° C.

Provenance & Evidence