Preparation and determination of configuration of 3-halogeno-3-methyl-5α-cholestane epimers

Abstract

3α-Chloro-3β-methyl- and 3β-chloro-3α-methyl-5α-cholestane were prepared by reaction of hydrochloric acid with the two epimeric 3-hydroxy-3-methyl-5α-cholestanes. A better yield and cleaner conversion could be obtained with tetramethyl-1-chlorovinylamine as chlorinating agent. Reaction of the two 3-methyl-5α-cholestanols with triphenylphosphine–carbon tetrachloride or phosphorus trichloride oxide–pyridine gave mixtures of 3-methyl-5α-cholest-2-ene, 3-methyl-5α-cholest-3-ene, and 3-methylene-5α-cholestane. The two epimeric 3-fluoro-3-methyl-5α-cholestanes were obtained by treatment of the two 3-methyl-5α-cholestan-3-ols with (diethylamino)sulphur trifluoride. The configuration of the 3-halogeno-3-methyl-5α-cholestanes was determined from their ¹³C n.m.r. spectra. The availability of both 3-halogeno-3-methyl-5α-cholestane epimers allowed an unambiguous interpretation of the i.r. spectra in the 800–400 cm^–1 region.