Method for preparing betamethasone ketal by homogeneous reaction at normal temperature

Abstract

The invention provides a novel method for preparing betamethasone ketal by homogeneous reaction at normal temperature, which comprises the steps of: adding reagents of dichloromethane, triethyl orthoformate and boron fluoride etherate in a normal temperature homogeneous system; carrying out condensation reaction through Platts oxides and ethanediol to prepare betamethasone ketal; reacting for 2-15h, condensing filtrate again, extracting semi-condensed materials, and again putting the materials. The product content is not less than 90 percent and the yield is 115-118 percent. Compared with thetraditional process, the method has the advantages of shortening the reaction time, improving the content and the yield of the betamethasone ketal, reducing the environment pollution, discarding the benzene with huge hurt on the human body and the environment, ensuring that the production process is more environmentally friendly, lowering the labor intensity of workers, generating better social benefit, and being more beneficial to the massive industrialized production.

Description

technical field [0001] The invention belongs to the technical field of steroid hormone drug synthesis, and relates to a production method of an important intermediate ketal product of the steroid hormone betamethasone. Background technique [0002] Betamethasone is an important glucocorticoid drug, which has anti-inflammatory, anti-allergic, anti-toxin, and anti-shock effects. It can improve the adaptability and tolerance of antibodies during stress reactions, so as to reduce the damage of various factors to antibodies. It has inhibitory effect on inflammation caused by various reasons, can relieve the symptoms of immune response, resist bacterial endotoxin damage to the body, and can increase the reactivity of blood vessels to adrenaline drugs, increase blood pressure and improve microcirculation. Compared with dexamethasone, its anti-inflammatory effect is stronger than that of dexamethasone, triamcinolone, and hydrocortisone, with less side effects. [0003] Betamethason...

AI Technical Summary

Problems solved by technology

[0007] There are some defects in the traditional preparation method: first, the water-carrying efficiency of benzene is low, and benzene equivalent to 25-40 times of the substrate must be used, and it must be carried out under high-temperature reflux at about 80 ° C, in the form of azeotrope Take the water produced by the reaction out of the system

This has just caused many negative results: First, there will be a large amount of benzene leaking into the production workshop and the surrounding atmospheric environment, which will cause great harm to the human body and the environment; second, benzene can only dissolve the substrate but not well Miscibility with ethylene glycol makes the reaction system a heterogeneous system, which slows down the reaction speed, prolongs the reaction time, and incomplete reaction; third, the reflux temperature is higher, far exceeding the temperature required for the condensation reaction, making the side effect The quality of the reaction increases and the yield decreases; the fourth is that although the product is mainly soluble in the benzene layer, a small part is also soluble in ethylene glycol, and this part of the product cannot be recovered, resulting in a further reduction in the reaction yield; the fifth is that it takes a long time to work, High energy consumption; Sixth, the catalytic effect of p-toluenesulfonic acid is not ideal, and it is not the best catalyst

In addition, in the above heterogeneous system, the probability of contacting and colliding with the substrate mainly in ethylene glycol is very small, resulting in a further reduction in the catalytic effect

Finally, the post-processing process is very cumbersome, the operability is poor, and the labor intensity is high, resulting in large fluctuations in various indicators

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