A kind of preparation method of cinacalcet hydrochloride
A technology of cinacalcet hydrochloride and cinnamic acid, which is applied in the preparation of organic compounds, the preparation of amino compounds, chemical instruments and methods, etc., can solve the problems of high processing cost, low yield, cumbersome reaction steps, etc., and achieve product impurities. The effect of low content, simplified operation steps and stable product quality
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Embodiment 1
[0048] The preparation method of cinacalcet hydrochloride is as follows:
[0049] (A) Using 25 kg of trifluoromethyl cinnamic acid as a raw material, 2.5 kg of palladium carbon as a catalyst, and 150 L of methanol as a solvent, carry out hydrogenation reduction at a temperature of 0-60 ° C for 1-24 h to obtain a yellow oil Fluoromethylphenylpropionic acid, yield 98.0%;
[0050] (B) Condensation reaction of m-trifluoromethylphenylpropionic acid and R-(1)naphthylethylamine at a mass ratio of 1:4 at a temperature of 50-200°C for 1-20h to obtain an off-white solid ( R)-N-(1-(naphthalene-1-yl)ethyl)-3-(trifluoromethyl)phenyl)propionamide, the yield was 92.1%;
[0051] (C) (R)-N-(1-(naphthalene-1-yl)ethyl)-3-(trifluoromethyl)phenyl)propanamide and acetic acid in a mass ratio of 10:1 at a temperature of 0- Cinacalcet was obtained as a yellow oil after being reduced by the reducing agent boron trifluoride at 10°C, the solvent used was tetrahydrofuran, and the yield was 98.2%;
[00...
Embodiment 2
[0054] The preparation method of cinacalcet hydrochloride is as follows:
[0055] (A) Add 50kg of trifluoromethyl cinnamic acid, 0.5kg of palladium carbon and 150L of N,N-dimethylformamide in the autoclave, first replace the nitrogen with nitrogen twice, then replace the nitrogen twice with hydrogen, pass Add hydrogen to keep the pressure at 0.2-0.3MPa, carry out hydrogenation and reduction at a temperature of 30°C for 4 hours, stop stirring, evacuate, discharge and filter, wash with 20L of methanol, and concentrate the filtrate to dryness under vacuum at 40°C. Obtain 49.6 kg of yellow oil m-trifluoromethylphenylpropionic acid, yield 98.0%;
[0056] (B) Condensate 45kg of m-trifluoromethylphenylpropionic acid and 14kg of R-(1)naphthylethylamine at a temperature of 140°C for 5h, stop heating and add ethyl acetate when cooling to 40-60°C 100L, 30L of water, separated after stirring, the water phase was extracted once with 40L of ethyl acetate, the organic phase was combined, an...
Embodiment 3
[0061] The preparation method of cinacalcet hydrochloride is as follows:
[0062] (A) Add 50kg of trifluoromethylcinnamic acid, 0.25kg of palladium carbon and ethanol and N,N-dimethylformamide mixture 150L in the autoclave, wherein the mass percentage of palladium in the catalyst is 5 -10%, first replace nitrogen twice with hydrogen, then replace nitrogen twice with hydrogen, feed hydrogen to maintain the pressure of 0.2-0.3MPa, carry out hydrogenation and reduction at a temperature of 40°C for 10h, stop stirring, empty and discharge Filter, wash with 20L of methanol, and concentrate the filtrate to dryness at 40°C to obtain 48.6kg of m-trifluoromethylphenylpropionic acid as a yellow oil, with a yield of 98.0%;
[0063] (B) Condensate 45kg of m-trifluoromethylphenylpropionic acid and 36kg of R-(1)naphthylethylamine at a temperature of 150°C for 6h, stop heating and add ethyl acetate when cooling to 40-60°C 100L, 30L of water, separated after stirring, the water phase was extr...
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