CN104402764A - Preparation method for entacapone - Google Patents

Abstract

The invention discloses a preparation method for entacapone. The preparation method comprises the following steps: 3, 4-dyhydroxyl-5-nitrobenzaldehyde, N, N-diethyl cyanoacetamide, piperidine and acetic acid are added into isopropanol to be subjected to heating backflow reaction, and finally the reactants are subjected to recrystallization in the isopropanol, so that the entacapone is prepared. The prepared entacapone has excellent quality and high purity, and the preparation method is simple, low in energy consumption and low in cost.

Description

A kind of preparation method of Entacapone

 

Technical field

The present invention relates to a kind of preparation method of pharmaceutical raw material, specifically a kind of preparation method of Entacapone.

Background technology

Entacapone (entacapone) is a specific peripheral catecholamine-O-methyltransferase inhibitors (COMTI, catechol-O-methyltransferase), is a kind new medicine of Orion development and production, and trade(brand)name comtan(jade-like stone is red).Within 1998, in listings such as Britain, Germany, Denmark, more than 70 the countries and regions listing in the whole world so far, E is used for the assisting therapy of Parkinson's disease (PD), is the adjuvant drug of levodopa.

Summary of the invention

The technical problem to be solved in the present invention is to provide a kind of preparation method of Entacapone, and its cost is low, and yield is high, and Z isomer content is low.

Technical scheme of the present invention is:

A preparation method for Entacapone, comprises the steps:

(1), first Virahol is joined in reaction vessel, and then by 3,4-dihydroxyl-5-nitrobenzaldehyde, N, N-diethylcyanoacetamide, piperidines, acetic acid join reflux 2.5-3.5h in reaction vessel, after reaction terminates, reaction solution are cooled to room temperature, and gained throw out is at room temperature stirred spend the night, finally be cooled to 0-5 DEG C, after filtration, washing, vacuum-drying, obtain Entacapone piperidinium salt;

(2), the Entacapone piperidinium salt that step (1) obtains is joined in Virahol under 20-30 DEG C of condition, is cooled to 0-5 DEG C, then filters, washs, vacuum-drying, obtain product.

The mass ratio of 3,4-dihydroxyl-5-nitrobenzaldehydes, N, N-diethylcyanoacetamide, piperidines, acetic acid and Virahol in described step (1) reaction vessel is 1: 1.50-1.55: 0.65-0.75: 0.45-0.55: 7.5-8.5.

Washing in described step (1) adopts washed with isopropyl alcohol.

The concrete steps of washing adopt volume ratio to be Virahol and the water washing of 1:2 in described step (2), finally washes with water.

Advantage of the present invention:

Entacapone quality prepared by the present invention is good, and purity is high, and preparation method is simple, and less energy consumption, cost is low.

Embodiment

A preparation method for Entacapone, comprises the steps:

(1), first 700ml Virahol is joined in reaction vessel, and then by 70g 3,4-dihydroxyl-5-nitrobenzaldehyde, 107gN, N-diethylcyanoacetamide, 48.8g piperidines, 34.4g acetic acid join reflux 2.5-3.5h in reaction vessel, after reaction terminates, reaction solution are cooled to room temperature, and gained throw out is at room temperature stirred spend the night, finally be cooled to 0-5 DEG C, after filtration, 140ml washed with isopropyl alcohol, vacuum-drying, obtain Entacapone piperidinium salt;

(2), the Entacapone piperidinium salt that step (1) obtains is joined in 600ml Virahol under 20-30 DEG C of condition, be cooled to 0-5 DEG C, Virahol and the water washing of then filtering, adopting 240ml volume ratio to be 1:2, finally wash with water, vacuum-drying, obtains product.

Claims (4)

1. a preparation method for Entacapone, is characterized in that, comprises the steps:

(1), first Virahol is joined in reaction vessel, and then by 3,4-dihydroxyl-5-nitrobenzaldehyde, N, N-diethylcyanoacetamide, piperidines, acetic acid join reflux 2.5-3.5h in reaction vessel, after reaction terminates, reaction solution are cooled to room temperature, and gained throw out is at room temperature stirred spend the night, finally be cooled to 0-5 DEG C, after filtration, washing, vacuum-drying, obtain Entacapone piperidinium salt;

(2), the Entacapone piperidinium salt that step (1) obtains is joined in Virahol under 20-30 DEG C of condition, is cooled to 0-5 DEG C, then filters, washs, vacuum-drying, obtain product.

2. the preparation method of a kind of Entacapone according to claim 1, it is characterized in that: in described step (1) reaction vessel 3, the mass ratio of 4-dihydroxyl-5-nitrobenzaldehyde, N, N-diethylcyanoacetamide, piperidines, acetic acid and Virahol is 1: 1.50-1.55: 0.65-0.75: 0.45-0.55: 7.5-8.5.

3. the preparation method of a kind of Entacapone according to claim 1, is characterized in that: the washing in described step (1) adopts washed with isopropyl alcohol.

4. the preparation method of a kind of Entacapone according to claim 1, is characterized in that: the concrete steps of washing adopt volume ratio to be Virahol and the water washing of 1:2 in described step (2), finally washes with water.