Novel method for preparing (2r)-2-(2-methoxyphenyl)-2-(oxane-4-yloxy)ethane-1-ol compound, and intermediate used therein

Patent metadata

Field	Value
Publication number	US-2020283401-A1
Application number	US-201816650981-A
Country	US
Kind code	A1
Filing date	Sep 27, 2018
Priority date	Sep 28, 2017
Publication date	Sep 10, 2020
Grant date	—

Abstract

A novel method for preparing a compound of Chemical Formula 1 is disclosed. The method includes a step of obtaining a compound of Chemical Formula 1 by performing a reduction reaction on a compound of Chemical Formula 2; and an intermediate used therein. According to the preparation method of the present invention, the compound of Chemical Formula 1, which is useful for the production of an acetyl-CoA carboxylase (ACC) inhibitor, can be mass-produced more simply and efficiently than that of a conventional method:

First claim

1 . A method for preparing a compound of Formula 1 below comprising a step of performing a reduction reaction on a compound of Formula 2 below to obtain the compound of Formula 1:

2 . The method for preparing the compound of Formula 1 according to claim 1 , wherein the reduction reaction is performed using at least one selected from the group consisting of lithium aluminum hydride (LiAlH 4 ,LAH), borane dimethyl sulfide (BH 3 S(CH 3 ) 2 ,BMS), lithium borohydride (LiBH 4 ), aluminum hydride (AlH 3 ), and RED-AL (Vitride).

3 . The method for preparing the compound of Formula 1 according to claim 1 , wherein the compound of Formula 2 is prepared by comprising a step of neutralizing a compound of Formula 3 below in the presence of an acid, and then extracting to obtain the compound of Formula 2 from an organic layer:

4 . The method for preparing the compound of Formula 1 according to claim 3 , wherein the neutralization of the compound of Formula 3 is carried out using at least one acid selected from the group consisting of hydrochloric acid, nitric acid, sulfuric acid, acetic acid, and trifluoroacetic acid.

5 . The method for preparing the compound of Formula 1 according to claim 3 , wherein the compound of Formula 3 is prepared by comprising a step of producing a salt from a compound of Formula 4 below and a compound of Formula 8 below:

6 . The method for preparing the compound of Formula 1 according to claim 5 , wherein in the production of the salt, at least one solvent selected from the group consisting of methanol, ethanol, isopropanol, acetonitrile, toluene, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl acetate, ethyl acetate, isopropyl acetate, and diethyl ether is used.

7 . The method for preparing the compound of Formula 1 according to claim 6 , further comprising a step of adding the mixed solvent obtained by mixing water with the solvent used to form the salt to the already obtained salt compound, warming to the reflux temperature of the mixed solvent while stirring, and cooling it to room temperature and then purifying the reprecipitated solid by filtration, after producing the salt from the compound of Formula 4 and the compound of Formula 8.

8 . The method for preparing the compound of Formula 1 according to claim 5 , wherein the compound of Formula 4 is prepared by comprising a step of hydrolyzing a compound of Formula 5 below in the presence of a base:

9 . The method for preparing the compound of Formula 1 according to claim 8 , wherein the hydrolysis is carried out using at least one base selected from the group consisting of potassium carbonate, calcium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, lithium hydroxide, and sodium hydrogen carbonate.

10 . The method for preparing the compound of Formula 1 according to claim 8 , wherein the compound of Formula 5 is prepared by comprising a step of introducing a leaving group to a compound of Formula 6 below and performing a substitution reaction with a compound of Formula 7 below:

11 . The method for preparing the compound of Formula 1 according to claim 10 , wherein the leaving group is introduced by adding at least one selected from the group consisting of methanesulfonyl chloride, toluenesulfonyl chloride, benzenesulfonyl chloride, chlorine (Cl 2 ), bromine (Br 2 ), iodide (I 2 ), oxalyl chloride ((COCl) 2 ), thionyl chloride (SOCl 2 ), and sulfuryl chloride (SO 2 Cl 2 ) to the reaction solution.

12 . A compound represented by Formula 2 below which is an intermediate of the compound of Formula 1 according to claim 1 :

13 . A compound represented by Formula 3 below which is an intermediate of the compound of Formula 1 according to claim 1 :

14 . A compound represented by Formula 4 below which is an intermediate of the compound of Formula 1 according to claim 1 :

15 . A compound represented by Formula 5 below which is an intermediate of the compound of Formula 1 according to claim 1 :

Assignees

• Hanmi Pharm Ind Co Ltd

Inventors

• Jang Wook
• Baek Jong Ouk
• Kim Hee Cheol
• Ha Tae Hee

Classifications

• C07D309/10 Primary

  Oxygen atoms · CPC title

• A61K31/351

  not condensed with another ring · CPC title

• C07D309/12 Primary

  only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers · CPC title