An improved synthesis of (24R)-3β-(2H-Tetrahydropyran-2-yloxy)cholesta-5,7-diene-24,25-diol – a key intermediate in the synthesis of (24R)-24,25-dihydroxyvitamin D3

A multistep procedure for the conversion of ergosterol into the tetrahydropyranyl ether of (24R)-24,25-dihydroxyprovitamin D₃ using 1,4-dihydrophthalazine-1,4-dione as diene protecting agent was compared with an established route, which uses 4-phenyl-1,2,4-triazoline-3,5-dione for the protection of the diene system. The disclosed reaction sequence allows to double the overall yield. The 1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2,3-ylene group proved to be the better diene protecting group in the ozonolytic degradation of the ergosterol side chain. Maintaining the protecting group in the next reaction steps offered further advantages by diminishing the air and light sensitivity of the intermediates.