SYNTHESIS OF CHOLESTEROL AND VITAMIN D3 FROM PHYfOSTEROLS

A process for manufacture of Vitamin D3 from phytosterols, comprising:

• a) manufacturing cholesterol by:
• treating a phytosterol with a p-toluene sulfonyl halide in a first base to obtain a phytosteryl tosylate;
• treating the phytosteryl tosylate with methanol in a second base to obtain a phytosteryl-1-methyl ether;
• treating the phytosteryl-1-methyl ether with ozonized oxygen in a first solvent at a temperature range of −50° C. to −90° C., followed by treatment with a reducing agent at a temperature range of −40° C. to 0° C. to obtain (20S)-20-hydroxymethyl-6β-methoxy-3α,5-cyclo-5α-pregnane;
• tosylating the (20S)-20-hydroxymethyl-6β-methoxy-3α,5-cyclo-5α-pregnane with a tosylating agent in a third base to obtain (20S)-6-methoxy-20-(p-toluene sulfonoxy methyl)-3α,5-cyclo-5α-pregnane;
• subjecting the (20S)-6-methoxy-20-(p-toluene sulfonoxy methyl)-3α,5-cyclo-5α-pregnane to a Grignard reaction by treatment with a reaction product of magnesium and isopentyl bromide in a first ether solvent in the presence of a CuBr·Me2S catalyst to obtain i-cholesteryl methyl ether;
• and
• hydrolyzing the i-cholesteryl methyl ether in aqueous dioxane with catalytic amounts of PTSA at a temperature of 70-90° C. to obtain cholesterol;
• b) converting the cholesterol into cholesteryl acetate by treating the cholesterol with acetic anhydride in the presence of a fifth base at a temperature ranging from 30° C. to 70° C.;
• c) brominating the cholesteryl acetate with a brominating agent in a first hydrocarbon solvent to obtain 7-bromo cholesteryl acetate, followed by treating the 7-bromo cholesteryl acetate with TBAF in a second ether solvent at a temperature ranging from 10° C. to 30° C. to obtain 7-dehydrocholesterol acetate;
• d) subjecting the 7-dehydrocholesterol acetate to alkaline hydrolysis in an alcoholic solvent at about 30° C. to 60° C. to obtain 7-dehydrocholesterol;
• and
• e) converting the 7-dehydrocholesterol into vitamin D3 by irradiating the 7-dehydrocholesterol under a high-pressure mercury lamp in a fourth solvent in the presence of a sensitizer.