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Preparation of cinacalcet hydrochloride

IP.com Disclosure Number: IPCOM000238567D
Publication Date: 2014-Sep-04
Document File: 1 page(s) / 50K

Publishing Venue

The IP.com Prior Art Database

Related People

Andrés E. Lukach: AUTHOR [+4]

Abstract

Provided is a process for the preparation of cinacalcet hydrochloride from 3-[3-(trifluoromethyl)phenyl]propanal and (R)-(+)-1-(1-napthyl)ethylamine

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Preparation of cinacalcet hydrochloride

(R)-N-[1-(1-naphthyl)ethyl]-3-[3-(trifluoromethyl)phenyl]propan-1-amine hydrochloride, also known as cinacalcet hydrochloride, has the following chemical structure:

Provided is a process for its preparation from 3-[3-(trifluoromethyl)phenyl]propanal and (R)-(+)-1-(1-napthyl)ethylamine via reductive amination with sodium borohydride, followed by hydrochloride formation and crystallization:

A catalytic amount of water was added to a mixture of 3-[3-(trifluoromethyl)phenyl]propanal and (R)-(+)-1-(1-napthyl)ethylamine in a cooled alcohol as the reaction solvent. Then, sodium borohydride was carefully added. The reaction was monitored by HPLC for several hours in order to complete the process.

Then, more water was added and the alcohol was distilled at reduced pressure. An organic solvent was added and the pH was adjusted at 6 using concentrated hydrochloric acid. The mixture was stirred and separated. The organic layer was additionally washed with aqueous hydrochloric acid and separated. The organic layer was dried, filtered through Celite in hot, partially concentrated and cooled at 0 °C to achieve precipitation of crude product.

The obtained crude product was recrystallized from an organic solvent, and was filtered and dried in vacuum oven to afford dry cinacalcet hydrochloride, having more than 99% purity.