Industrial production method of 5 alpha-androst-2-ene-17-one

Abstract

The invention discloses an industrial production method of 5 alpha-androst-2-ene-17-one. The method comprises the following steps of: dissolving epiandrosterone p-toluenesulfonates into a monomethylpyridine solvent, carrying out beta-elimination reaction within a certain temperature range, and removing p-toluenesulfonates to obtain the 5 alpha-androst-2-ene-17-one. The industrial production method has the advantages of simple and easily-obtained raw materials, simplicity and convenience in operation, no 3,4-double bond isomerization impurities in the finally-obtained product, safety in production, high yield and little pollution from three wastes so as to be suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of organic chemistry, and specifically relates to an industrialized preparation method of 5α-androst-2-en-17-one, which comprises performing β-elimination reaction of epiandrosterone p-toluenesulfonate in a monomethylpyridine solvent. De-tosylate yields 5α-androst-2-en-17-one. Background technique [0002] 5α-Androst-2-en-17-one is a synthetic cyclic thiosterol, the antiarrhythmic drug Orudin and non-depolarizing steroidal muscle relaxants such as Pancuronium, Vecuronium, Picuronium Common intermediates of ammonium, rocuronium bromide, etc. [0003] Rocuronium Bromide (Rocuronium Bromide) and Vecuronium Bromide (Vecuronium Bromide) are new monoquaternary ammonium steroids in time-acting muscle relaxants, used as adjuvant drugs for anesthesia, used for endotracheal intubation and muscle relaxation during surgery, with onset effect Fast, short duration, no accumulation, no tachycardia and blood pressure changes, no re...

AI Technical Summary

Problems solved by technology

The boiling point of 2,4,6-collidine is 171°C at normal pressure. In industrial production, steam heating is not easy to reach the reflux temperature, the production operation is difficult, and it cannot be industrialized; 2,4,6-Collidine is irritating, and its Acute toxicity LD50 is 400 mg / kg (oral for rats), 1000-2000 mg / kg (percutaneous for guinea pigs), not suitable for industrial application; 2,4,6-collidine Expensive and expensive to produce

2,6-lutidine, also known as 2,6-lutidine, also known as 2,6-dimethylazabenzene, is highly irritating and can damage the nervous system, liver, and kidneys. Eyes, skin and mucous membrane irritation symptoms occur, and cause headache, dizziness, nausea, vomiting, mental retardation, abdominal pain, diarrhea, etc., which are unfavorable to the health of operators; Steam heating is not easy to reach the reflux temperature, the production operation is difficult, and it is not easy to industrialize

The freezing point of dimethyl sulfoxide is 18.4°C, and it solidifies at room temperature lower than 18.4°C. As a solvent for industrial production, it needs to be melted before being used for feeding after solidification, and the operation is cumbersome; its normal pressure boiling point is 189°C, and it is not easy to recover; Strong hygroscopicity, when the relative humidity is 60% at 20°C, it can absorb moisture equivalent to 70% of its own weight from the air, and it is very difficult to recycle it into low-moisture dimethyl sulfoxide; it is corrosive to iron metal when it contains water , corrosive to production equipment and pipelines; irritating and sensitizing, unfavorable to the health of operators; and this method directly uses thermal cracking, which is easy to form 3,4-double bond isomers, and the direct crystallization product still contains A small amount of 3,4-double bond isomers

[0017]In a word, most of the methods for preparing 5α-androst-2-en-17-one at present use toxic solvents, which are cumbersome to operate, complicated to deal with, and easy to produce 3,4-double bond isomer impurity and difficult to purify, expensive, not particularly suitable for industrial production

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