Synthesis of tetraethyl ester of 5-aminothiophene by phase transfer catalysis was written by Hu, Kai;Ding, Xiang-Yu;Jia, Xiang-Man;Jiang, Ye;Liu, Feng-Hua. And the article was included in Zhongguo Xiandai Yingyong Yaoxue in 2008.Reference of 58168-20-0 This article mentions the following:
A method for the synthesis of the title compound [i.e., tetra-Et ranelate; 5-[bis(2-ethoxy-2-oxoethyl)amino]-4-cyano-2-(ethoxycarbonyl)-3-thiopheneacetic acid] is reported here. The synthesis of this tetra-Et ester of 5-aminothiophene was achieved by a by phase transfer catalyzed reaction and the best reaction conditions were determined Cyclization of 3-oxopentanedioic acid 1,5-di-Et ester with propanedinitrile and sulfur provided 5-amino-4-cyano-2-(ethoxycarbonyl)-3-thiopheneacetic acid Et ester. Then in acetone, tetra-Et ester of 5-aminothiophene was synthesized from 5-aminothiophene by phase transfer catalysis with Et bromoacetate in presence of a crown ether using potassium carbonate as solid base. Under optimized reaction conditions, crown ether was used as phase transfer catalyst, the molar ratio of alkylating reagent, alkali and reagent was 2.2 and 2.5 resp., the reaction temperature was 60° and the reaction time was 6 h. This method provides high product yield and purity. This is a key intermediate for strontium ranelate (a bone formation stimulant). In the experiment, the researchers used many compounds, for example, Ethyl 5-amino-4-cyano-3-(2-ethoxy-2-oxoethyl)thiophene-2-carboxylate (cas: 58168-20-0Reference of 58168-20-0).
Ethyl 5-amino-4-cyano-3-(2-ethoxy-2-oxoethyl)thiophene-2-carboxylate (cas: 58168-20-0) belongs to nitriles. There has been no report on the microbial biosynthesis of nitriles and the physiological function of such enzymes, nor was it not even known whether aliphatic and aromatic nitriles are biological compounds or just petrochemicals. Nitrile groups in organic compounds can undergo a variety of reactions depending on the reactants or conditions. A nitrile group can be hydrolyzed, reduced, or ejected from a molecule as a cyanide ion.Reference of 58168-20-0
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts