Diethyl Malonate → Diethyl 2-(methylthio)benzyl-malonate
Reaction equation
O=S(Cl)Cl.[CH3:5][S:6][C:7]1[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=1[CH2:9]Cl.[C:15]([O:23][CH2:24][CH3:25])(=[O:22])[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18]>>[CH3:5][S:6][C:7]1[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=1[CH2:9][CH:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:15]([O:23][CH2:24][CH3:25])=[O:22]Participants
Procedure
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.
Sources & evidence
- ORD record
- ord-b23bb1a14e30478daea79b16cc1c7d88
- Source dataset
- uspto-grants-1993_12
- Patent number
- US05270313
Reaction notes
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