Development of a New Process for Tulobuterol Hydrochloride

Abstract

Tulobuterol is a selective β2-adrenoceptor agonist and has been widely utilized as a therapeutic agent for the treatment of asthma. Synthesis of tulobuterol has achieved many important progresses over the past decades and has gradually become one of the research hotspots in organic chemistry. This study aimed to explore a novel synthesis route to synthesize tulobuterol hydrochloride (1), an active ingredient of Chlobamolie Hydrochloride Tablets. In the study, 1 was obtained from the cost-effective, commercially available 2-chloroacetophenone through the key steps including the reactions of bromination, NaBH₄ reduction, and amination. Process-related impurities were also investigated. 1 was obtained with excellent purity (99.96%) in 53% overall yield without the need for chromatographic purification. The developed method is green, facile, and cost-effective; thus, it is suitable for the industrial-scale production of 1.

Keywords

tulobuterol hydrochloride - 2-chloroacetophenone - synthesis process

^# These two authors contributed equally to this work and should be considered co-first authors.

Supporting Information

¹H NMR and ¹³C NMR spectra of compounds 3, 1, 6, 7, 8, 9, 10, and 11, as well as HPLC results for the purities of compounds 3 and 1, are included in the Supporting Information ([Figs. S1]–[S18] [online only]).

Publikationsverlauf

Eingereicht: 07. Dezember 2022

Angenommen: 15. Februar 2023

Artikel online veröffentlicht:
16. März 2023

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