Synthetic process of 3-chloro-octahydro-2(1h)-quinolinone

Abstract

The invention discloses a synthesis technology of 3-chloro-octahydro-2(1H)-quinolinone. In a solvent, the 3-chloro-octahydro-2(1H)-quinolinone is used as a raw material, zinc powder and sulfuric acid are used as a reducing agent, a reaction is performed at the temperature of 0-50 DEG C for 2-6 h, a water phase is separated out, an organic phase is concentrated, a recrystallization solvent is added for stirring, and filtering and drying are performed to obtain the 3-chloro-octahydro-2(1H)-quinolinone. The synthesis technology is significantly characterized in that activation energies required by two chlorine atom reduction reactions are much different, and the reactions can be easily controlled in the single-chlorine reduction stage just by strictly controlling the reaction temperature and selecting the proper mixing solvent and the proportions thereof. Due to the fact that a series of side reactions are inhibited, the influence on the reaction time is small, and the high conversion rate is easily ensured. Due to the fact that few influence factors of the technology exist, the control conditions are mold, the technology is easily magnified, large-scale production is achieved, and guarantees on the multiple aspects of cost, quality and the like are provided for transolapril commercialized marketing.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a synthesis process of 3-chloro-octahydro-2(1H)-quinolinone. Background technique [0002] 3-Chloro-octahydro-2(1H)-quinolinone is an important intermediate of a new drug for hypertension—Trandolapril (Trandolapril), and it is the most critical factor affecting the preparation cost of Trandolapril. Puli's core steps. So far, two documents published abroad are 3-chloro-octahydro-2(1H)-quinolinone prepared from 3,3-dichloro-octahydro-2(1H)-quinolinone, these two documents Using the same process route: [0003] [0004] The method disclosed in US4933361 is: 15.9g of 3,3-dichloro-octahydro-2(1H)-quinolinone is dissolved in ethanol solution, 10ml of triethylamine is added, the catalyst is Raney nickel, at 20~25℃ After the reaction, concentrate the reaction solution, extract the residue twice with ethyl acetate and water, dry the organic phase with anhydrous sodium sulfate, fil...

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Problems solved by technology

[0009] 2. Since the series of side reactions in the above-mentioned hydrogenation reduction reaction process are difficult to control, the lower reaction conversion rate has to be controlled

[0010] 3. Due to the double impact of poor selectivity and low conversion rate, it is difficult to improve the quality of the product, which has obvious negative effects on subsequent reactions.

[0011] 4. Since the above-mentioned reaction process control needs to take into account both selectivity and conversion rate, there are many factors affected, and it is difficult to achieve the results of the small test in the process of process amplification, which makes the process difficult to stabilize, resulting in high production costs.

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