Preparation method for (R)-3-([1,1'-biphenyl]-4-radical)-2-aminopropionic-1-alcohol hydrochloride

Abstract

The invention relates to a preparation method for (R)-3-([1,1'-biphenyl]-4-radical)-2-aminopropionic-1-alcohol hydrochloride. The preparation method for the (R)-3-([1,1'-biphenyl]-4-radical)-2-aminopropionic-1-alcohol hydrochloride comprises the steps that (S)-1-([1,1'-biphenyl]-4-radical)-3-chloropropyl-2-alcohol is dissolved by methylbenzene, triphenyl phosphine and succinimide are added under the protection of nitrogen gas, 0-5 DEG C temperature keeping is carried out, a methyl benzene solution of diisopropyl azodicarboxylate is added, and the temperature is kept for a reaction for 2-8 hours; feed liquid is subjected to decompression drying by distillation, water and hydrochloric acid are added, the mixture is heated to micro-backflow, and stirring is carried out for 16 hours or longer while the temperature is kept; and reaction liquid stands for skimming, products in a water phase and products in an organic phase in the reaction liquid are purified through organic solvents, drying is carried out for 8 hours or longer at the temperature ranging from 50 DEG C to 60 DEG C, and the product is obtained. According to the method, the process is simple, few impurities exist in the product, the yield is high, the amount of the raw materials is small, the production cost of the product can be remarkably reduced in large-scale production, generation of waste is reduced, and the ecological environment is protected. The solvents used in the purification process of the product are easy to recycle, and the treatment cost is greatly reduced.

Description

technical field [0001] The invention belongs to the field of synthesis of pharmaceutical intermediates, in particular to a preparation method of (R)-3-([1,1'-biphenyl]-4-yl)-2-aminopropan-1-ol hydrochloride . Background technique [0002] (R)-3-([1,1'-biphenyl]-4-yl)-2-aminopropan-1-ol hydrochloride is an important drug intermediate, for example, it is a drug for heart failure drug LCZ696 Synthetic intermediate, its molecular structural formula is as follows: [0003] [0004] However, there are very few relevant literature reports about the synthesis of (R)-3-([1,1'-biphenyl]-4-yl)-2-aminopropan-1-ol hydrochloride in the existing technology. It is even more rare, and in fact the production cost and product quality of (R)-3-([1,1'-biphenyl]-4-yl)-2-aminopropan-1-ol hydrochloride are directly related to The manufacturing cost and drug quality of the final drug such as LCZ696. Contents of the invention [0005] Aiming at the defects in the prior art, the present inven...

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Problems solved by technology

[0004] However, there are very few relevant literature reports about the synthesis of (R)-3-([1,1'-biphenyl]-4-yl)-2-aminopropan-1-ol hydrochloride in the existing technology. It is even more rare, and in fact the production cost and product quality of (R)-3-([1,1'-biphenyl]-4-yl)-2-aminopropan-1-ol hydrochloride are directly related to Preparation cost and drug quality of final drug such as LCZ696

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