A kind of preparation method of bazedoxifene acetate

Abstract

The invention discloses a preparation method of bazedoxifene acetate. The method is characterized in that raney nickel is used as a catalyst, and a compound I and hydrogen react in a microreactor to obtain bazedoxifene under the conditions that the temperature is 20 to 40DEG C and the hydrogen pressure is controlled to be 0.1 to 0.5Mpa. According to the method, the raney nickel with lower price is used to replace expensive palladium carbon, so that the production cost is effectively reduced, the microreactor is used and the production is in streamline operation; an obtained product is high in yield and good in quality; the preparation method has the advantages of high reaction efficiency, mild reaction conditions, safe and controllable operation, short reaction time and low cost; the method is easier for industrial production (The formula is shown in the description).

Description

technical field

[0001] The invention relates to a preparation method of bazedoxifene acetate, which belongs to the technical field of medicine. Background technique

[0002] Bazedoxifene is a new generation of selective estrogen receptor modulator (SERM), which can competitively inhibit the binding of 1713-estradiol to estrogen receptors ERoc and ER13, and has estrogen agonists on bone Active, can improve the bone density of the spine and hip, so it can significantly reduce the risk of vertebral fractures in postmenopausal women with osteoporosis. Its structural formula is as follows:

[0003]

[0004] There are many synthetic methods of bazedoxifene, but at present most of the synthetic methods all prepare 1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-5-benzyloxy Base-2-(4-benzyloxy-phenyl)-3-methyl-1H-indole, and then debenzyl protection by hydrogenation reduction to obtain bazedoxifene. Most of the debenzylation methods in this route use palladium carbon catalytic hydrogenati...

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