Cinacalcet IMpurity synthesis

Yield:-

Reaction Conditions:

with hydrogen;Raney-Ni in methanol at 75 - 80; under 8826.87 - 11033.6 Torr; for 16 h;

Steps:

14
Example 14; Preparation of (R)-α-methyl-N-[3-[3-(trifluoromethyl)phenyl]propyl]-l-(5,6,7,8- tetrahydronaphthalene)methane amine hydrochloride (Tetrahydro Cinacalcet hydrochloride) A solution of cinacalcet base (15 g) in methanol (150 ml) was hydrogenated with raney-Ni catalyst (10 g) at 12-15 kg pressure at 75-8O⁰C for 16 hours. The catalyst was filtered off and the filtrate was concentrated under vacuum at below 50⁰C to get crude product (16 g). The crude product was crystallized from heptane (100 ml) to obtain the free base of tetrahydro cinacalcet. The base was dissolved in acetonitrile (25 ml) and a mixture of concentrated hydrochloric acid (3 g) and water (50 ml) was added at 25-3O⁰C. The reaction mixture was cooled to 0-5⁰C and the precipitated product was filtered and washed with water and then dried under vacuum at 45-50⁰C to provide 0.75 g of tetrahydro cinacalcet hydrochloride (Purity by HPLC: 96.5%).

References:

ACTAVIS GROUP PTC EHF;SEBASTIAN, Sonny;PERI, Seetha, Rama, Sarma;RAMAMURTHY, Katikireddy;PRADHAN, Nitin, Sharadchandra WO2010/67204, 2010, A1 Location in patent:Page/Page column 46