Synthesis method of vitamin D3 intermediate 7-ketocholesteryl acetate

Abstract

The invention discloses a synthesis method of a vitamin D3 intermediate 7-ketocholesteryl acetate, and relates to 7-ketocholesteryl acetate. The method comprises the following steps: adding cholesteryl acetate to a mixed solvent, introducing oxygen as an oxidant, adding a main catalyst and a nonmetal cocatalyst, carrying out a catalytic allylic oxidation reaction, and purifying the obtained reaction product to obtain the vitamin D3 intermediate 7-ketocholesteryl acetate. No complex post-treatment processes are needed; a quaternary ammonium salt is adopted as the cocatalyst, so decomposition of peroxides is effectively promoted; tetrahydrofuran azeotropic water removal is adopted to remove water generated in the decomposition process of the peroxides, so the decomposition is complete, and the reaction is fast and mild; and he main catalyst and the cocatalyst are nonmetal catalysts respectively, and are cheap and easily available, the main catalyst can be reused 5 or more times, the conversion rate and the selectivity are respectively high, and the reaction yield reaches 85% or above, so the synthesis method has the advantages of high efficiency and low cost.

Description

technical field [0001] The invention relates to 7-ketocholesterol acetate, in particular to a synthesis method of vitamin D3 intermediate 7-ketocholesterol acetate. Background technique [0002] 7-ketocholesterol acetate is an important precursor of vitamin D3 intermediate 7-dehydrocholesterol, and 7-ketocholesterol acetate can be obtained in high yield by hydrazone, dehydrazone and saponification. [0003] The synthesis of 7-ketocholesteryl acetate involves the oxidation of the allyl position. The traditional method is to use chromium salt as the oxide, mainly including chromium oxide, PDC, sodium dichromate, potassium dichromate, etc., but the chromium salt is When the oxidizing agent is used, its consumption is large, and the post-treatment is too complicated, and heavy metals cause serious environmental pollution, so it is difficult to be widely used. [0004] Another common method is to use peroxides as oxidizing agents, such as tert-butanol peroxide and hydrogen perox...

AI Technical Summary

Problems solved by technology

[0003] The synthesis of 7-ketocholesteryl acetate involves the oxidation of the allyl position. The traditional method is to use chromium salt as the oxide, mainly including chromium oxide, PDC, sodium dichromate, potassium dichromate, etc., but the chromium salt is When the oxidant is used, the amount of it is large, and the post-treatment is too complicated, and the heavy metals cause serious environmental pollution, so it is difficult to be widely used

However, this method requires an equivalent level of oxidant, the cost is too high, and the safety of peroxide use has always been problematic, so this method is not suitable for industrial production

[0005] In recent years, with the development of green chemistry, there have been more and more reports on the use of oxygen to oxidize allylic sites under the catalysis of nitrogen oxides. Chinese patent CN101418030 uses heavy metal cocatalysts cobalt acetate and manganese acetate, N-hydroxy phthalate Formimide (NHPI) is a catalyst, oxygen oxidizes cholesterol acetate, and the reaction yield is improved to a better level, but the heavy metal co-catalyst used is relatively expensive, and cannot be recycled, and the cost is higher

Images