Synthesis method of (R)-3-chloropyridyl-2-trifluoroethylamine hydrochloride

Abstract

The invention discloses a synthesis method of (R)-3-chloropyridyl-2-trifluoroethylamine hydrochloride, and the synthesis method is characterized in that a Grignard reaction, a chiral induction addition reaction and a deprotection reaction are sequentially carried out to finally prepare a finished product. The invention provides a brand-new synthesis method of the (R)-3-chloropyridyl-2-trifluoroethylamine hydrochloride for the first time. The synthetic method is short in route, raw materials are easy to obtain, operation is easy, a continuous flow microreactor technology is adopted in the first step, reactants are rapidly and effectively mixed, the reaction time and the reaction temperature are accurately controlled, side reactions are avoided, and the conversion rate and safety are effectively improved. The compound 4 with high chiral purity is obtained through chiral induction addition reaction and recrystallization purification, and the de value of the compound 4 is greater than 99.5%. The post-treatment method is simple in post-treatment operation, column chromatography treatment is not needed after each step of reaction, reactants can be purified only through washing and extraction of a solvent, and the method is a novel post-treatment purification method.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis technology, specifically relates to a method for synthesizing (R)-3-chloropyridyl-2-trifluoroethylamine hydrochloride, and belongs to the field of synthesizing pharmaceutical intermediates. Background technique [0002] (R)-3-Chloropyridyl-2-trifluoroethylamine hydrochloride is an important intermediate, which plays an irreplaceable role in the synthesis of pharmaceuticals and pesticides. Molecular formula is C 7 h 7 Cl 2 f 3 N 2 , the molecular weight is 247.04, and the CAS number is 2089671-65-6. Calcium channels are transmembrane, multisubunit proteins that control Ca 2+ Enter the cell from the extracellular fluid. Almost all excitable cells in the human body, such as neurons of the central nervous system, peripheral nerve cells, and muscle cells, including cells of skeletal muscle, cardiac muscle, and smooth muscle of veins and arteries, have voltage-dependent calcium channels...

AI Technical Summary

Problems solved by technology

[0006] It can be seen from the market research results that the number of domestic and foreign suppliers of (R)-3-chloropyridyl-2-trifluoroethylamine hydrochloride is very limited, and there is no documented (R)-3-chloro The synthetic method of pyridyl-2-trifluoroethylamine hydrochloride, therefore, this area urgently needs a kind of preparation method of (R)-3-chloropyridyl-2-trifluoroethylamine hydrochloride

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