Process for the preparation of oseltamivir and its phosphate and intermediates thereof

By employing a novel synthetic route that utilizes a ring-opening reaction catalyzed by bases and Lewis acids, the use of hazardous reagents and precious metals is avoided, enabling the synthesis of oseltamivir and its phosphates with high stereoselectivity and low cost, making it suitable for industrial applications.

CN117105801BActive Publication Date: 2026-03-27SICHUAN QINGMU PHARMA CO LTD
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Patent Information

Application Number
CN202310907034.8
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2023-07-24
Publication Date
2026-03-27
Estimated Expiration
2043-07-24

AI Technical Summary

Technical Problem

Existing methods for synthesizing oseltamivir and its phosphates use hazardous reagents such as sodium azide and expensive precious metal catalysts, involve multiple reaction steps, have low overall yields, high costs, and pose risks for industrial production.

Method used

A novel synthetic route was adopted, in which the triethylammonium group of compound VIII undergoes a substitution reaction with the hydroxyl group of compound VII under alkaline conditions, followed by a ring-opening reaction with tert-butylamine under Lewis acid catalysis. Oseltamivir was obtained by acetylation and deprotection, avoiding the use of sodium azide and noble metal catalysts and employing milder reaction conditions.

Benefits of technology

The synthesis of oseltamivir and its phosphate with high stereoselectivity and low cost has been achieved. The route is short, the conditions are mild, and it is suitable for industrial production.

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Abstract

The application belongs to the technical field of pharmaceutical chemistry synthesis, and specifically discloses a preparation method of oseltamivir and a phosphate thereof and an intermediate thereof, which comprises the following steps: (1) a compound of formula VII is reacted with VIII under the action of a base in a solvent to obtain an intermediate of formula VI, and then the intermediate of formula VI is reacted under the action of a strong base at high temperature to obtain formula V; (2) formula V is subjected to ring-opening reaction with tert-butylamine in a solvent under the catalysis of a Lewis acid to obtain formula IV; (3) formula IV is reacted with an acetylating agent in a solvent under the action of a base to obtain formula III; (4) formula III is reacted under the action of an acid at a certain temperature to obtain formula II; and (5) formula II is subjected to salt formation with phosphoric acid in a solvent to obtain oseltamivir. The preparation method has the characteristics of simple operation, low cost, high yield, high optical purity of the product, stable process and the like, and is suitable for industrial production.
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