Process for preparing tert-butyl (3R,5S)-6-hydroxy-3,5--O--isopropylidene-3,5-dihydroxyhexanoate
AssigneeHoechst Aktiengesellschaft
InventorsGerhard Beck, Joachim-Heiner Jendralla, Kurt Kesseler
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Abstract
A novel process is described for preparing tert-butyl (3R, 5S ) 6-hydroxy-3,5-O-isopropylidene-3,5-dihydroxyhexanoate of the formula I ##STR1## which is a valuable structural element for preparing inhibitors of HMG-CoA reductase.
Claims2
A process for preparing tert-butyl (3R, 5S)-6-hydroxy-3,5-O-isopropylidene-3,5-dihydroxyhexanoate of the formula I, ##STR18## wherein ethyl .omega.-benzyloxyacetoacetate of the formula II ##STR19## wherein Bn is benzyl is asymmetrically hydrogenated to give ethyl 2(S)-hydroxy-3-benzyloxybutyrate of the formula III, ##STR20## the .beta.-hydroxy ester of the formula III is converted by means of a Claisen condensation with ##STR21## into the .beta.-keto-.sigma.-(S)-hydroxy ester of the formula IV, ##STR22## the resultant ester of the formula IV is converted by diastereoselective reduction into tert-butyl 3(R), 5(S)-dihydroxy-6-benzyloxyhexanoate of the formula V, ##STR23## the hydroxyl groups in the dihydroxy ester of the formula V are protected, with the formation of the acetonide of the formula VI, ##STR24## and the benzyl protective group is removed from the acetonide of the formula VI, with the formation of the compound of the formula I;
- wherein the asymmetric hydrogenation of compound II to give compound III is carried out
- a) at a substrate/catalyst molar ratio substantially greater than 1000:1,
- b) using an in-situ ruthenium(II) chloride-(R)-BINAP catalyst, and
- c) under a hydrogen pressure of less than 5 atm H.sub.2.
Dependencies are inferred from the claim text.