Methyl iodide → Methyl 5-(3-azidobutyl)thiophene-2-carboxylate

Participants

Reaction Steps

For the preparation of the amine starting material of Example 7,4-(5-acetyl-2-thienyl)-2-butanone was reacted with ethylene glycol, triethyl o-formate and p-toluenesulfonic acid in methylene chloride selectively to give methyl 5-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-2-thienyl ketone. Oxidation with sodium hypobromite and subsequent hydrolysis gave 5-(3-oxobutyl)-2-thiophenecarboxylic acid. With sodiumborohydride there was obtained therefrom 5-(3-hydroxy-butyl)-2-thiophenecarboxylic acid which was converted in dimethylacetamide with methyl iodide and sodium bicarbonate into the methyl ester. Treatment with p-toluene-sulfonyl chloride in pyridine and reaction with sodium azide in dimethylsulfoxide gave methyl 5-(3-azidobutyl)-2-thiophenecarboxylate from which the corresponding acid was obtained by saponification. With thionyl chloride there was prepared its acid chloride from which, with concentrated ammonia in diethyl ether, there was obtained 5-(3-azidobutyl)-2-thiophenecarboxamide. Reduction of the azido group with triphenylphosphine and subsequent hydrolysis gave (R,S)-5-(3-aminobutyl)-2-thiophenecarboxamide, m.p. 65°-75°, ε256 =7780, ε275 =9900.

Provenance & Evidence