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 preparation of a compound of formula 7, or a derivative thereof, wherein PG1 is an alcohol protecting group, the process comprising: nucleophillic addition of an allyl-silane derivative of formula 8 to a compound of formula 4 to form the compound of formula 5; wherein R1 is a alcohol protecting group, and each R2, R3 and R4 independently is an alkyl, cyclo-alkyl, aryl or hetero-aryl group; deprotecting the compound of formula 5 under conditions to remove the R′ protecting group , and protecting the resulting aldehyde to form a compound of formula 6, wherein each R5 and R6 independently is an alkyl, cyclo-alkyl, aryl or hetero-aryl group, optionally having one or more heteroatoms, or R5 and R6 together form an alkanediyl group, optionally having one or more heteroatoms; replacing the hydroxyl group with a methylene group in the compound of formula 6, followed by deprotection of the protected aldehyde to form the compound of formula 7;