An Efficient Method for Preparation of Diltiazem

Autor:	Tomiki Hashiyama
Rok vydání:	1999
Předmět:	chemistry.chemical_compound Chemistry Organic Chemistry chemistry.chemical_element Reactivity (chemistry) Stereoselectivity Diltiazem hydrochloride Lewis acids and bases Tin Benzene Medicinal chemistry Oxygen Catalysis
Zdroj:	Journal of Synthetic Organic Chemistry, Japan. 57:394-400
ISSN:	1883-6526 0037-9980
DOI:	10.5059/yukigoseikyokaishi.57.394
Popis:	An efficient method for preparation of diltiazem hydrochloride, a representive calcium antagonist widely used for the treatment of ischemic heart disease all over the world, is described. In the reaction of 2-nitrothiophenol (1) with trans-3-phenylglycidic esters (2) carrying various substituents on the benzene ring, both reactivity and stereoselectivity of the oxirane ring-opening of the glycidates were markedly influenced by the electronic nature of the substituents. As a result of our investigation on the catalytic effect of various Lewis acids in the reaction of 2a with 1, tin compounds were found to be effective catalysts for the cis-opening and readily produced the threo-nitro ester (3a), a key intermediate for the synthesis of diltiazem.Isolation of the crystalline complex from the reaction of 1 with SnCl4 and its efficient catalytic activity similar to that of SnCl4 suggest that the transition state involves co-cordination of tin derivatives both with 1 and the epoxy oxygen of 2a to result in highly specific cis-opening.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::adf1b3a84516114f60ec2fc0b128a92b https://doi.org/10.5059/yukigoseikyokaishi.57.394 Zobrazit plný text záznamu