PROCESS FOR PREPARING ALBUTEROL, ACETAL, HEMI-ACETAL, AND HYDRATES OF ARYLGLYOXAL INTERMEDIATES THEREOF

摘要

Preparing acetals and hemi-acetals of formulas (VII) or (V) <IMG> and <IMG> wherein Ar represents aryl or substituted aryl; R represents alkyl, substituted alkyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heterocyclic or heterocyclic alkyl and R3 represents hydrogen, alkyl, aryl or substituted aryl, comprising contacting a compound of formula (II): <IMG> wherein Ar and R3 are as defined above and L is a leaving group, with a sulfoxide and an alcohol of the formula ROH wherein R is as defined above, or alternatively, contacting a compound of formula (I): <IMG> wherein Ar and R3 are as defined above, with a halogenating agent, a sulfoxide, and an alcohol of formula ROH wherein R is as defined above, to give the acetal or hemi-acetal of formula (VII) or (V). Preparing glyoxal hydrates of formula: <IMG> wherein Ar and R3 are as defined above by hydrolyzing an acetal or hemi-acetal of formulas (VII) and (V), respectively. Acetals and hemi-acetals of the formula: <IMG> wherein Z is -NH2, -OH or -OR6, where R6 represents hydrogen or alkyl of one to ten carbon atoms, and R7 and R8 independently represent hydrogen, alkyl, substituted alkyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heterocyclic or heterocyclic alkyl with the proviso that only one of R7 or R8 is hydrogen, or R7 and R8 together with the oxygen atom forms a five or six membered ring. These intermediates are useful for preparing arylethanolamines, especially albuterol.