A kind of preparation method of α-abortion-3,5-cracking-androst-5-one-3,17-dioic acid

Abstract

The invention provides a preparation method of A-nor-3, 5-cracking-androstane-5 -keto-3, 17-diacid. The preparation method comprises the following steps: (1), 3-carbonyl-4-androstene-17beta carboxylic acid is dissolved in alkaline water, and the temperature of the solution is controlled to be 20-40 DEG C; (2), an oxidizing agent which is an aqueous solution including sodium periodate and potassium permanganate is added, and reaction is performed continuously for 1-3 h after addition; (3), after sufficient reaction, cooling is performed by ice brine until the temperature is 0-5 DGE C, spin-filtering is performed, and a filter cake is washed by ice alkaline water at the temperature of 0-5 DEG C and spin-dried; and (4), a filtrate obtained from spin-filtering is acidized and spin-filtered, and a filter cake is washed until an eluate is neutral. According to the provided method, an organic solvent is not used, accordingly, the method is economic and environment-friendly, and aftertreatment is simple; reaction is performed under homogeneous phase condition, the reaction temperature and iodate separation temperature are lower, the product quality is good, the yield is high, the iodate recovery rate is high, and the cost is low. Therefore, a product with higher purity can be obtained at high yield and low cost with the method.

Description

technical field [0001] The invention belongs to the field of organic chemistry, and in particular relates to a preparation method of carbocyclic compounds. Background technique [0002] The pharmaceutical intermediates for the preparation of dutasteride (dutasteride, 1) include A-abortion-3,5-cleavage-androst-5-one-3,17-dioic acid, which can be obtained from commercially available 3-carbonyl-4- Androstene-17β carboxylic acid comes from oxidative ring opening, and its general reaction formula is as follows: [0003] [0004] The current traditional production method introduced in the literature is: with 3-carbonyl-4-androstene-17β carboxylic acid methyl ester or 3-carbonyl-4-androstene-17β carboxylic acid amide as substrate, with tert-butanol, water Mixed solvent, sodium carbonate as alkali catalysis, sodium periodate and potassium permanganate aqueous solution oxidation (US20060046994A1; CN101863956A). Traditional production methods have the following defects: [0005]...

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Problems solved by technology

Therefore, the temperature of rejection filtration before acidification is higher, so that the precipitation of iodate is reduced, and the recovery rate is reduced. At the same time, because the price of iodate is relatively expensive, the water temperature of washing is too high to lose iodine salt, and the water temperature of washing is too low. Then the sodium salt of entrained A-abortion-3,5-cracking-androst-5-one-3,17-dioic acid in the iodate filter cake will increase, and the product will be lost

[0008] Therefore, the traditional production method consumes a lot of solvent, the recovery rate of iodate is low, the quality is poor, the yield is low, the cost is high, and the pollution of "three wastes" is large

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