Method for preparing Prasugrel intermediate alpha-cyclopropylcarbonyl-2-fluorobenzyl bromide

Abstract

The invention discloses a new method for preparing a Prasugrel intermediate alpha-cyclopropylcarbonyl-2-fluorobenzyl bromide which is a compound shown as a formula (III). In the method, a compound shown as a formula (I), namely cyclopropyl-2-fluorobenzyl ketone is taken as a raw material, and is bromized by a compound show as a formula (II), namely phenyltrimethylammonium tribromide to form the target product of alpha-cyclopropylcarbonyl-2-fluorobenzyl bromide, namely the compound in the formula (III). The method has the advantages of mild reaction conditions, high selectivity, high yield, low cost and environmental friendliness, and is suitable for large-scale industrial production.

Description

Method for preparing prasugrel intermediate α-cyclopropylcarbonyl-2-fluorobenzyl bromide Technical field The invention belongs to the field of medicine and chemical industry, and specifically relates to a preparation method of prasugrel intermediate α-cyclopropylcarbonyl-2-fluorobenzyl bromide. Background technique Prasugrel is a tetrahydrothienopyridine compound similar to clopidogrel. It has the advantages of platelet aggregation inhibitory effect, good oral absorption, strong metabolic activity and weak toxicity. Clinical Phase III shows superior activity, tolerability and safety than clopidogrel, so it is a promising antithrombotic drug. At present, the preparation methods of prasugrel mainly include EP192535, EP542411, US4740510, US5288726, US5874581, WO04098713, CN101250193, CN92111584, CN10117743, etc. Among all the disclosed methods, α-cyclopropylcarbonyl-2-fluorobenzyl bromide (formula III) is an important intermediate indispensable for the preparation of prasugrel. ...

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Problems solved by technology

In the disclosed patents at present, the preparation of α-cyclopropylcarbonyl-2-fluorobenzyl bromide all adopts bromine or N-bromosuccinimide (NBS) as the bromination reagent, and bromine will produce a large amount of Hydrobromic acid, while NBS also uses bromine in the process of recovery and reuse. At the same time, it also has low selectivity, low product yield, high cost, difficult recycling of bromine, low product purity, and difficult separation and purification. and other shortcomings, which lead to the above two brominated reagents having many disadvantages in terms of operational safety, environmental protection, economy, etc.

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