Process for preparation of 3-((2s,5s)-4-methylene-5-(3-oxopropyl)tetrahydrofuran-2-yl)propanol derivatives and intermediates useful thereof

摘要

Discloses is a process for preparation of a compound of formula 7, or a derivative thereof, wherein PG1 is an alcohol protecting group. Also, disclosed are intermediates and processes for their preparation. The compound of formula 7 can be useful in the preparation of halinchondrin analogs such as Eribulin.;

主权项

1. A process for the preparation of compound of formula 4, where PG1 is an alcohol protecting group, the process comprising:
converting the hydroxyl group of compound of formula 1 into a leaving group (LG), hydrolyzing the 5,6-isopropylidene protecting group and oxidatively cleaving the diol to form the aldehyde of formula 2; reacting the compound of formula 2 with a base to eliminate the leaving group (LG), followed by reacting the resulting alkene with Ph3P═CHCO2Me (9), or an analog thereof, to form the compound of formula 3; and hydrogenating the alkene, reducing the ester functional group to an alcohol and protecting the resulting alcohol to form the compound of formula 4.