Method for synthesizing 3beta-hydroxy-16alpha,17alpha-epoxy-5-pregnene-20-ketone

Abstract

The invention discloses a method for synthesizing 3beta-hydroxy-16alpha,17alpha-epoxy-5-pregnene-20-ketone, which comprises the following steps of: adding 348.8 weight parts of methanol into 7.0 weight parts of diene, and heating to the temperature of 40 DEG C with stirring; reducing the temperature to be between 26 and 27 DEG C, and adding 68.7 weight parts of 30 percent H2O2, 34.3 weight parts of 10 percent NaOH, 22.9 weight parts of 30 percent H2O2 and 11.4 weight parts of 10 percent NaOH slowly; controlling the temperature to be between 28 and 30 DEG C in the process of adding liquid, raising the temperature to be between 34 and 35 DEG C, keeping the temperature, reacting for 3 to 4 hours, and distilling under reduced pressure to obtain a white solid; and washing the white solid, performing suction filtration, leaching, and drying at the temperature of 105 DEG C to obtain a high-purity oxygen-bridged object. In the method, a synthetic process is short in time, oxygen-bridged reaction is complete, a melting point of the product is stabilized between 189.5 and 191.2 DEG C, the content of the product is 99.3 percent, and the yield of the product is between 98.5 and 99.1 percent. The method is suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and relates to a synthesis method of 3β-hydroxyl-16α, 17α-epoxy-5-pregnene-20-one, specifically a 3β-hydroxyl-16α, 17α- Improved method for the synthesis of epoxy-5-pregnene-20-one. Background technique [0002] 3β-Hydroxy-16α, 17α-epoxy-5-pregnene-20-one is also called oxygen bridge or 16,17α-epoxypregnenolone, which is important for the synthesis of steroid corticosteroids and steroid progesterone The intermediate is an important process raw material for the production of Woshi oxide, and the quality of Woshi oxide is directly controlled by the quality of the oxygen bridge. [0003] 3β-Hydroxy-16α, 17α-epoxy-5-pregnene-20-one in the traditional synthesis process basically needs 18 hours of synthetic reaction time, while the yield of oxygen bridge is only about 90%, and the melting point is Around 185°C, the content is 96-97%. For improving yield and purity, people have done a lo...

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Problems solved by technology

For improving yield and purity, people have done a lot of efforts, and the Chinese patent that notification number is CN101717426A discloses a kind of synthetic method of oxygen bridge, wherein used sodium silicate complexing agent, makes the content of oxygen bridge by 95% Increased to 99.0%, the melting point reached 185 ° C, and the yield of the finished product increased by 2 percentage points, but the sodium silicate in the reaction system brought troubles to the subsequent processing of the product, increased the process, and made it unsuitable for large-scale industrial production ; Published in "Acta Molecular Sciences" magazine 2007 volume 23 No. 3 literature "synthesis and characterization of epoxy pregnenone", adjusted the consumption of reagent by laboratory test, namely: dienolone acetate ( mol): 30%H 2 o 2 (L): 10% NaOH (L) is 1: 6: 3, reacts at room temperature for 2h, makes oxygen bridge product yield reach 92%, and fusing point is 147-149 ℃, the progress of this method is that reaction is carried out at room temperature, And improved the productive rate, but the defective that exists is, product melting point is lower, and content is unstable, and the consumption of hydrogen peroxide and sodium hydroxide is also bigger; European patent PCT No: 2004021975 from (-)-3β-hydroxyl-5 - Pregnene-20-one uses sodium hydroxide and hydrogen peroxide with methanol and water as solvents, reacts at 5-15 ° C for 13 hours, and the yield of oxygen bridges can reach 99%, but in this process, methanol water is used as a solvent. Low temperature reaction takes a long time, which increases the production cost and is not conducive to factory production

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