Process Development of Tacalcitol

A highly convergent, gram-scale synthesis of vitamin D3 analogue tacalcitol 1 is disclosed, starting from L-valine and Inhoffen–Lythgoe diol. Key features of the synthesis include modified Julia olefination reaction of β-oxybenzothiazol-2-yl sulfone with C/D ring containing aldehyde to access decagrams of fully functionalized C/D ring synthon. The Horner–Wadsworth–Emmons (HWE) reaction between the C/D ring fragment and commercially available phosphonate completes the carbo-skeleton, which is elaborated into tacalcitol 1 in a gram-scale synthesis.