Demethylation of 4-Methoxyphenylbutyric Acid Using Molten Pyridinium Hydrochloride on Multikilogram Scale

Autor:	Michael A. Staszak, Jason S. Cronin, Christopher A. Beck, Schmid Christopher Randall
Rok vydání:	2004
Předmět:	Solvent chemistry.chemical_compound Chemistry Hydrochloride Organic Chemistry Extraction (chemistry) Organic chemistry Pyridinium Physical and Theoretical Chemistry Stoichiometry Demethylation
Zdroj:	Organic Process Research & Development. 8:670-673
ISSN:	1520-586X 1083-6160
Popis:	4-Methoxyphenylbutyric acid (2) is smoothly demethylated in 3 h at 180 °C when melted with pyridinium hydrochloride (Pyr·HCl), affording 4-hydroxyphenylbutyric acid (3), a key starting material for the preclinical candidate LY518674 (1). The adaptation of this chemistry to 22-L and pilot-plant scale is described, including findings to facilitate product isolation, selection of a compatible extraction solvent, and observation of an unusual relationship between the number of solvent extractions and the Pyr·HCl stoichiometry. To the best of our knowledge, this represents the first literature report of the use of this classic demethylation chemistry on multikilogram scale.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::6d744140b2f2d1c4707b55603160c0d4 https://doi.org/10.1021/op0499526 Zobrazit plný text záznamu