Preparation method of cyclopentyl phenyl ketone

Abstract

The invention provides a preparation method of cyclopentyl phenyl ketone.The preparation method includes hydrolyzing 2-cyclopentyl benzoylacetate as a raw material in basic solvents to obtain a product, namely the cyclopentyl phenyl ketone, wherein the 2-cyclopentyl benzoylacetate is 2-cyclopentyl methyl benzoylacetate or 2-cyclopentyl ethyl benzoylacetate.The preparation method of the cyclopentyl phenyl ketone has the advantages of environment-friendly solvents, little environmental pollution, easiness in operation, high yield, short technological period and low preparation cost.

Description

technical field [0001] The invention belongs to the technical field of medicines, and in particular relates to an efficient preparation method of phenylcyclopentyl ketone, a key intermediate of penhyclidine hydrochloride. Background technique [0002] Penehyclidinehydrochloride (PCHE) is a new class 1 anticholinergic drug, which is mainly used for administration before anesthesia to inhibit the secretion of salivary glands and airway glands, the first-aid treatment of organophosphate poisoning (pesticide) poisoning, and the late stage of poisoning or Cholinesterase (ChE) maintains atropine after aging. [0003] Phenylcyclopentyl ketone is a key intermediate for the synthesis of penhyclidine hydrochloride, and its structure is as follows: [0004] The existing synthesis techniques are: [0005] 1. The synthesis method reported by Tetrahedron Letters, 2006, 47, 7749-7753: [0006] This route generates cyclopentyl titanate at low temperature with titanate and cyclopentyl mag...

AI Technical Summary

Problems solved by technology

[0020] This route can be with the synthetic phenylcyclopentyl ketone of medium yield with cheap raw material benzaldehyde, but this route needs in nitrogen (N 2 ) protection, microwave assistance, difficult operation, not suitable for industrial production and the reaction needs to be reacted at high temperature (180°C), the cost of industrial production is high, and it is not easy to scale up production

[0021] To sum up, the limitations of the synthetic routes reported in the existing literature are: Grignard reagents are used to prepare secondary alcohols or phenylcyclopentyl ketone directly, and the reaction needs to be carried out at a low temperature of -78°C. Very harsh; metal (AlCl 3 、Ru 3 (CO) 12 , Pd(OAc) 2 , Cu(OAc), Cp*Ru(PN)) catalyzed method, the source of raw material itself needs to be prepared under harsh conditions such as Grignard reaction, and the product inevitably produces heavy metal residues

High temperature and high pressure have very high requirements on equipment, and the cost has increased significantly, and the catalyst itself is expensive, highly toxic, and difficult to store, etc.