Preparation method of medical intermediate 6-amino heliotropin

Abstract

The invention discloses a preparation method of a medical intermediate 6-amino heliotropin, wherein the method comprises the following steps: S1, adding heliotropin into concentrated nitric acid to react, and pouring into water; S2, extracting with an organic solvent, and collecting an organic phase; S3, adding potassium permanganate into the organic phase, reacting at the temperature of 90-120 DEG C, filtering to remove solids, and collecting filtrate; and S4, adding a palladium-carbon catalyst into the filtrate, reducing at the temperature of 80-100 DEG C in the presence of a mixed gas of hydrogen and inert gas to obtain a crude product, and recrystallizing the crude product. Compared with the prior art, the preparation method has the advantages that the purification step of an intermediate product is omitted; the yield of the final product 6-amino heliotropin is about 40-50%, so that the raw material utilization rate is remarkably improved, the operation efficiency of enterprises isimproved, the time cost and the material cost are saved for the enterprises, and the method has a wide industrial prospect.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a preparation method of a pharmaceutical intermediate 6-aminopiperonal. Background technique [0002] Quinoline and its derivatives, as the core components of drugs, have important applications in human antimalarial. In recent years, people have synthesized quinoline and its various derivatives, which are combined with various proteins / amino acids as carriers, and have the characteristics of precise targeted delivery, low toxicity and high loading capacity. As someone reported, the amino acid-8-aminoquinoline plays an important role in eradicating recurrent Plasmodium vivax and Plasmodium ovale, and can effectively kill gametophytes and sporophytes, and it is difficult for Plasmodium to have resistance to this drug. Medicinal properties. With the increasing application of quinoline drugs in antimalarial, the demand for quinoline compounds is also on the rise. [00...

AI Technical Summary

Problems solved by technology

[0007] However, this synthetic method has relatively large disadvantages, which are mainly reflected in: in the step of nitration of piperonal to 6-nitropiperonal, the oxidizing agent used is concentrated nitric acid, which has strong oxidizing properties; and the aldehyde base itself is Reductive active groups are easily oxidized by concentrated nitric acid to generate by-products other than 6-nitropiperonal, and by-products account for a relatively large proportion of the final product, accounting for about 40-50% of the product Therefore, it inevitably leads to a reduction in the yield of the product; and the polarity of the by-product is equivalent to that of 6-nitropiperonal, so it is also difficult to separate, and the yield of 6-nitropiperonal obtained in this step is only About 50%; then 6-nitropiperonal is reduced to this step of 6-aminopiperonal, the reducing agent that adopts is iron, and obtained productive rate also only has about 60%

Therefore, the total yield of these two-step reactions is only 30%, which greatly consumes a large amount of raw material costs and time costs, and also hinders the large-scale application of 6-aminopiperonal, and also increases the production costs of enterprises.

[0008] Therefore, it is urgent to find a new method for preparing 6-aminopiperonal to solve the problems that the existing final product production yield is low and the production cost is high.

Images