PROCESS FOR PREPARING TERT-BUTYL (3R,5S)-6-HYDROXY-3,5-O- ISOPROPYLIDENE-3,5-DIHYDROXYHEXANOATE

摘要

Process for preparing tert-butyl (3R,5S)-6-hydroxy-3,5-O-isopropylidene-3,5-dihydroxyhexanoateA novel process is described for preparing tert-butyl(3R,5S)6-hydroxy-3,5-O-isopropylidene-3,5-dihydroxyhexan-oate of the formula I(See formula I)which is a valuable structural element for preparinginhibitors of HMG-CoA reductase. In particular, thepresent invention relates to a process for preparing thecompound of the formula I, wherein ethyl .omega.benzyloxyacetoacetate of the formula II(See formula II)is asymmetrically hydrogenated at substrate/catalyst molarratio greater than 1000:1, using an in-situ ruthenium (II)chloride -(R)-BINAP catalyst and hydrogen pressure of lessthan 5 atm H2 to give ethyl 2(S)-hydroxy-3-benzyloxybutyrateof the formula III,the .beta.-hydroxy ester of the formula III is converted by meansof a Claisen condensation into the .beta.-keto-.delta.-(S)-hydroxyester of the formula IV,the resultant ester of the formula IV is converted bydiastereoselective reduction into tert-butyl 3(R),5(S)-dihydroxy-6-benzyloxyhexanoate of the formula V,the hydroxyl groups in the dihydroxy ester of the formula Vare protected, with the formation of the acetonide of theformula VI,and the benzyl protective group is removed from theacetonide of the formula VI, with the formation of thecompound of the formula I.