An Improved Synthesis of 24,24-Difluoro-1α,25-dihydroxyvitamin D3 from Readily Available Vitamin D2

Abstract

An improved synthesis of a highly potent vitamin D3 analog, 24,24-difluoro-1α,25-dihydroxy vitamin D3 (lb) has been accomplished via vitamin D2-SO2 adducts. The introduction of fluorine atoms was performed by treating the a-keto ester (11) with diethylaminosulfur trifluoride. The total yield was 12.5% from inexpensive vitamin D2 in 11 steps. This sequence is sufficiently straightforward to be conducted on a gram scale. © 1995, The Pharmaceutical Society of Japan. All rights reserved.