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Updated: Oct 2, 2026

Synthesis of High Purity Nonsymmetric Dialkylphosphinic Acid Extractants
Published on: October 19, 2017
Efficient synthesis of the A-ring phosphine oxide building block useful for 1 alpha,25-dihydroxy vitamin D(3) and
Andrzej R Daniewski1, Lisa M Garofalo, Stanley D Hutchings
1Chemical Synthesis - Process Research, Non-Clinical Development, Pre-Clinical Research and Development, Hoffmannminus signLa Roche, Inc., Nutley, New Jersey 07110, USA.
Abstract:
The 1 alpha-hydroxy A-ring phosphine oxide 1, a useful building block for vitamin D analogues, was synthesized from (S)-carvone in nine synthetic operations and a single chromatographic purification in 25% overall yield. The synthesis features two novel efficient synthetic transformations: the Criegee rearrangement of alpha-methoxy hydroperoxyacetate 10 in methanol to obtain directly the desired secondary 3 beta-alcohol 11 and the highly chemo- and stereoselective isomerization of dieneoxide ester (E)-7 to the 1 alpha-allylic alcohol with an exocyclic double bond (E)-8. Further insight into the selectivity control of the latter rearrangement was obtained from the reactions of (Z)-epimeric substrates. The new synthetic approach leading to the 1 alpha-hydroxy epimers complements our previously reported synthesis of the corresponding 1 beta-epimers, thus producing all stereoisomers of these versatile building blocks efficiently from carvone.
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