Thionyl Chloride → Cinacalcet Impurity 74

Participants

Reaction Conditions

Reaction Steps

(R)-3-(1-(naphthalen-1-yl)ethylamino)-1-(3-(trifluoromethyl)phenyl)propan-1-ol hydrochloride (IX) (35.0 g, 85.393 mmol) is suspended in toluene (150 ml) at 20° C. and thionyl chloride (11.2 g, 94.141 mmol) is added slowly. The reaction mixture is stirred at 30°-40° C. for 4-5 hrs and then the solvent is distilled off under vacuum. The residual toluenic slurry is flushed with isopropanol, upon several distillation/refill cycles. The resulting isopropanol solution is refluxed for 1 hr, then cooled down to 45° C. and added with methyl tert-butyl ether (MTBE) (70 ml). The so-obtained suspension is stirred at 45° C. for 1 hr, then cooled down to 0° C. and aged 1 hr. 29.6 g of a 95.8:4.2 (HPLC % area) mixture of (R)-3-chloro-N-(1-(naphthalen-1-yl)ethyl)-3-(3-(trifluoromethyl)phenyl)propan-1-amine hydrochloride (X) and (R,E)-N-(1-(naphthalen-1-yl)ethyl)-3-(3-(trifluoromethyl)phenyl)prop-2-en-1-amine hydro-chloride (XI) is obtained as a white powder after filtration, washing with a 3:1 vol/vol isopropanol/MTBE mixture (2×20 ml) end exsiccation at 55° C. under vacuum.

Provenance & Evidence