阅读说明：本技术 一种（5-氟嘧啶-4-基）甲醇的合成方法 (Synthesis method of (5-fluoropyrimidine-4-yl) methanol ) 是由 史建云 王超 于 2020-06-16 设计创作，主要内容包括：本发明属于医药中间体,具体涉及一种(5-氟嘧啶-4-基)甲醇的合成方法。本发明以化合物A作为起始原料,通过在氧化剂作用下进行氧化,利用催化剂作用进行反应,从而得到(5-氟嘧啶-4-基)甲醇,本发明首次提供了一种(5-氟嘧啶-4-基)甲醇的合成方法,为(5-氟嘧啶-4-基)甲醇的合成方法提供了合成路线,且合成方法为路线简短,设计合理,且操作简单,易于控制。(The invention belongs to a medical intermediate, and particularly relates to a synthetic method of (5-fluoropyrimidin-4-yl) methanol. The invention takes the compound A as the initial raw material, and the compound A is oxidized under the action of an oxidant and reacts under the action of a catalyst to obtain the (5-fluoropyrimidin-4-yl) methanol, and the invention provides a synthetic method of the (5-fluoropyrimidin-4-yl) methanol for the first time, provides a synthetic route for the synthetic method of the (5-fluoropyrimidin-4-yl) methanol, and the synthetic method is short in route, reasonable in design, simple to operate and easy to control.)

1. A method for synthesizing (5-fluoropyrimidin-4-yl) methanol, which is characterized by comprising the following reaction formula:

comprises the following synthesis steps:

(1) putting the compound A, an oxidant, acid and methanol into a reactor, and heating and reacting under the protection of nitrogen to obtain a compound B;

(2) and putting the compound B, a catalyst, sodium acetate and a solvent into a reaction kettle, boosting the pressure, heating and reacting to obtain a compound C, namely (5-fluoropyrimidin-4-yl) methanol.

2. The method for synthesizing (5-fluoropyrimidin-4-yl) methanol according to claim 1, wherein the oxidizing agent in the step (1) is dibenzoyl peroxide.

3. The method for synthesizing (5-fluoropyrimidin-4-yl) methanol according to claim 1, wherein the acid in the step (1) is any one of trifluoromethanesulfonic acid, acetic acid, and methanesulfonic acid.

4. The method for synthesizing (5-fluoropyrimidin-4-yl) methanol according to claim 1, wherein in the step (1), the mass ratio of the compound A to the oxidizing agent to the trifluoroacetic acid is 1:1 to 3:2 to 4, and the solid-to-liquid ratio g/mL of the compound A to the methanol is 1:22 to 28.

5. The method for synthesizing (5-fluoropyrimidin-4-yl) methanol according to claim 1, wherein the catalyst in the step (2) is a palladium on carbon catalyst or a lindlar catalyst.

6. The method for synthesizing (5-fluoropyrimidin-4-yl) methanol according to claim 1, wherein the solvent in the step (2) is any one of ethanol, methanol, and propanol.

7. The method for synthesizing (5-fluoropyrimidin-4-yl) methanol according to claim 1, wherein in the step (2), the mass ratio of the compound B to the catalyst to the sodium acetate is 4-8: 2-3: 3-5, and the solid-to-liquid ratio g/mL of the compound B to the solvent is 1: 50-55.

Technical Field

The invention belongs to a medical intermediate, and particularly relates to a synthetic method of (5-fluoropyrimidin-4-yl) methanol.

Background

The synthesis method of the compound 5-fluoropyrimidin-4-yl) methanol and related derivatives have wide application in pharmaceutical chemistry and organic synthesis. At present, the synthesis method of 5-fluoropyrimidin-4-yl) methanol is only reported in documents. Therefore, it is necessary to develop a synthesis method which has easily available raw materials, convenient operation, easy control of reaction, proper overall yield and suitability for industrial production.

Disclosure of Invention

The technical problems to be solved by the invention are as follows: in view of the above-mentioned problems, the present invention provides.

In order to solve the technical problems, the invention adopts the following technical scheme:

a method for synthesizing (5-fluoropyrimidin-4-yl) methanol, comprising the following reaction formula:

；

comprises the following synthesis steps:

(1) putting the compound A, an oxidant, acid and methanol into a reactor, and heating and reacting under the protection of nitrogen to obtain a compound B;

(2) and putting the compound B, a catalyst, sodium acetate and a solvent into a reaction kettle, boosting the pressure, heating and reacting to obtain a compound C, namely (5-fluoropyrimidin-4-yl) methanol.

Preferably, the oxidizing agent in step (1) is dibenzoyl peroxide.

Preferably, the acid in the step (1) is any one of trifluoromethanesulfonic acid, acetic acid and methanesulfonic acid.

Preferably, the mass ratio of the compound A, the oxidant and the trifluoroacetic acid in the step (1) is 1: 1-3: 2-4, and the solid-to-liquid ratio g/mL of the compound A and the methanol is 1: 22-28.

Preferably, the catalyst in step (2) is a palladium carbon catalyst or a lindlar catalyst.

Preferably, the solvent in the step (2) is any one of ethanol, methanol and propanol.

Preferably, the mass ratio of the compound B, the catalyst and the sodium acetate in the step (2) is 4-8: 2-3: 3-5, and the solid-to-liquid ratio g/mL of the compound B and the solvent is 1: 50-55.

Compared with other methods, the method has the beneficial technical effects that:

(1) the invention provides a synthetic method of (5-fluoropyrimidin-4-yl) methanol for the first time, and provides a synthetic route for the synthetic method of (5-fluoropyrimidin-4-yl) methanol;

(2) the synthetic method of the (5-fluoropyrimidin-4-yl) methanol is short in route, reasonable in design, simple to operate and easy to control;

(3) the product obtained by the method has high yield.

Detailed Description

The invention is further illustrated by the following examples, without restricting its scope to these examples. Numerous other changes and modifications can be made by those skilled in the art without departing from the spirit and scope of the invention. In particular, certain agents which are both chemically and structurally related may be substituted for the agents described herein to achieve the same or similar results, and reactions may be carried out under conditions outside the preferred ranges, albeit less than optimally. Accordingly, such obvious substitutions and modifications are intended to be included within the scope of the appended claims.

The oxidant is dibenzoyl peroxide.

The acid is one of trifluoromethanesulfonic acid, acetic acid and methanesulfonic acid.

The catalyst is palladium carbon catalyst or Lindla catalyst.

The solvent is any one of ethanol, methanol and propanol.

A method for synthesizing (5-fluoropyrimidin-4-yl) methanol, comprising the following reaction formula:

；

comprises the following synthesis steps:

(1) taking materials according to the mass ratio of the compound A to the oxidant to the acid of 1: 1-3: 2-4 and the solid-to-liquid ratio g/mL of the compound A to the methanol of 1: 22-28, putting the compound A, the oxidant, the acid and the methanol into a reactor, and carrying out nitrogen protection, heating and reaction to obtain a compound B;

(2) taking the compound B, the catalyst and the sodium acetate according to the mass ratio of 4-8: 2-3: 3-5, wherein the solid-to-liquid ratio g/mL of the compound B to the solvent is 1: 50-55, putting the compound B, the catalyst, the sodium acetate and the solvent into a reaction kettle, boosting the pressure, heating and reacting to obtain a compound C, namely (5-fluoropyrimidin-4-yl) methanol.