Preparation method of 5a-androstane-2-ene-17-ketone

Abstract

The invention discloses a preparation method of 5a-androstane-2-ene-17-ketone. The method comprises the following two steps: (1) a supported heteropolyacid catalyst is prepared by adopting an impregnation method; and (2) epiandrosterone is refluxed in an organic solvent under the catalysis of the supported heteropoly acid catalyst to remove 3-hydroxyl to obtain 5a-androstane-2-ene-17-ketone and anisomer thereof, and a pure product of 5a-androstane-2-ene-17-ketone is obtained by recrystallization with ethanol. The yield can reach 90% or above, the HPLC is 98% or above, and green and environment-friendly industrial production can be achieved.

Description

technical field [0001] The present invention relates to a kind of preparation method of 5a-androst-2-en-17-one, this method comprises adopting impregnation method to prepare load-type heteropolyacid catalyst and epiandrosterone under the catalysis of load-type heteropolyacid catalyst and a Reflux in an organic solvent to remove the 3-hydroxyl group to obtain 5a-androst-2-en-17-one and its isomers, and recrystallize from ethanol to obtain its pure product. Background technique [0002] Steroid drugs have a variety of pharmaceutical activities, accounting for about 6% of the entire drug market, and the demand is increasing at a rate of 6%-10% every year. 5a-androst-2-en-17-one is an important raw material for the synthesis of steroidal drugs, such as tripcuronium bromide, vecuronium bromide, rocuronium bromide and thiosterol etc., therefore, for 5a-androst The research on the synthesis of -2-en-17-one is of great significance. [0003] At present, the synthesis methods repor...

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Problems solved by technology

[0003] At present, the synthesis methods reported at home and abroad mainly include: ⑴Johns W F, Mueller G P Theretropinacol rearrangement of 17ß-hydroxyandrostanes[J]. 17ß-hydroxyandrost-2-one described in J Org Chem, 1963, 28:1854-1856 was subjected to the action of boric acid at 310-380°C, and the product was obtained by high vacuum distillation; (2) Nagata W, Sugasawa T, Narisada M, eta1. Stemids and their o-2alkyl derivatives[J]. Chem Pharm BuR, 1966, 14: 174-186 reacted epiandrosterone and p-toluenesulfonyl chloride at room temperature to obtain p-toluenesulfonyl ester product, and then refluxed 2,4,6-collidine to obtain the target product; (3) left front Recently, Wu Laixi et al. Synthesis of 5a-androst-2-en-17-one[J]. "Industrial Catalysis" in December 2010, Volume 18, No. 12 described using epiandrosterone as a raw material, through benzenesulfonyl chloride sulfonylation, using 4-dimethylaminopyridine as a catalyst in dimethylformamide solvent to eliminate benzene Sulfonic acid, synthesized 5a-androst-2-en-17-one; these synthetic methods either have harsh reaction conditions, low yield, or expensive raw and auxiliary materials, and all need two-step reactions to complete