Concise synthesis of atorvastatin lactone under high-speed vibration milling conditions

Abstract

The Hantzsch-type sequential three-component reaction under high-speed vibration milling conditions between 4-methyl-3-oxo-N-phenylpentanamide, tert-butyl 2-[(4R,6R)-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetate and 1-(4-fluorophenyl)-2-iodo-2-phenylethanone in the presence of ytterbium triflate and silver nitrate, followed by hydrolytic deprotection/lactonization, afforded atorvastatin lactone in 38% overall yield, thus providing ready access to the top-selling antihyperlipidemic drug atorvastatin calcium.