Process for the preparation of 5-{2-[benzyl-(1-(4-hydroxyphenyl)-1-methylethyl)amino]-1-hydroxyethyl}benzene-1,3-diol hemifumarate

FR3148237B1Active Publication Date: 2025-10-17IND CHEM SRL
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Patent Information

Application Number
FR2024004346
Authority / Receiving Office
FR · FR
Patent Type
Patents
Current Assignee / Owner
Priority Date
2023-04-26
Filing Date
2024-04-25
Publication Date
2025-10-17
Estimated Expiration
2044-04-25

AI Technical Summary

Technical Problem

Existing methods for synthesizing fenoterol hydrobromide result in an unacceptable ratio of RR,SS to RS,SR isomers, leading to low industrial yield and the need for lengthy purification processes.

Method used

A process involving the preparation of a solution with a protic acid, reduction of the carbonyl function, treatment with a base, and precipitation of a hemifumarate salt, followed by purification to achieve a desired isomer ratio.

Benefits of technology

The process achieves a high yield of the RR,SS isomer, meeting European Pharmacopoeia specifications without requiring extensive purification, such as column chromatography or repeated crystallizations.

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Abstract

The present invention relates to a process for the industrial-scale preparation of 5-{2-[benzyl-(1-(4-hydroxyphenyl)-1-methylethyl)amino]-1-hydroxyethyl}benzene-1,3-diol hemifumarate, a salt consisting of two molecules of 5-{2-[benzyl-(1-(4-hydroxyphenyl)-1-methylethyl)amino]-1-hydroxyethyl}benzene-1,3-diol and one molecule of fumaric acid, having the following formula:5-{2-[benzyl-(1-(4-hydroxyphenyl)-1-methylethyl)amino]-1-hydroxyethyl}benzene-1,3-diol hemifumarate is a useful intermediate in the synthesis of 5-[(1RS)-2-[(1RS)-2-(4-hydroxyphenyl)-1-methylethyl]-amino-1-hydroxyethyl]benzene-1,3-diol hydrobromide, known in the pharmaceutical field under the common name fenoterol hydrobromide.
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