# US 11,306,076 B2 · Silibinin lipoic acid ester with hepatoprotective activity and a method of preparing the same

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- Number: US 11,306,076 B2
- Document ID: US11306076B2
- Status: Granted
- Kind: B2
- Application number: 16/871,354
- Filed: 2020-05-11
- Published: 2021-11-11
- Granted: 2022-04-19
- Earliest claimed: 2020-05-11
- Assignees: Xi'an Taikomed Pharmaceutical Technology Co., Ltd.
- Applicants: Yonghong Tang; Huafeng Qi; Peiyu Zhou; Xingke Ju; Chengyuan Liang; Yuzhi Liu; Bin Tian; Lei Tian; Gennian Mao; Limei Wang; Yuanyuan He; Yongbo Wang; Jingwen Xu; Dan Yang; Liang Qi; Wenbo Yao; Qianqian Zhao; Han Li
- Inventors: Yonghong Tang; Huafeng Qi; Peiyu Zhou; Xingke Ju; Chengyuan Liang; Yuzhi Liu; Bin Tian; Lei Tian; Gennian Mao; Limei Wang; Yuanyuan He; Yongbo Wang; Jingwen Xu; Dan Yang; Liang Qi; Wenbo Yao; Qianqian Zhao; Han Li
- Web page: https://patentgrep.com/patent/US11306076B2

## CPC

- C07D 409/14: containing three or more hetero rings
- B01J 27/24: Nitrogen compounds
- B01J 31/0238: {with a primary amino group}
- B01J 2231/49: Esterification or transesterification
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS

## Abstract

A compound having the formula (I): is disclosed. A method of preparing the compound of formula (I) is also disclosed.

## Claims

### Claim 1

A compound having the following formula (I):
wherein the compound is a mixture of two diastereomers and has a protective effect on alcoholic liver injury in mice and a concentration-dependent antioxidant activity.

### Claim 2 (depends on 1)

A method of preparing the compound of claim 1, comprising:
reacting a compound of formula (II) with a compound of formula (III) to obtain the compound of formula (I):

### Claim 3 (depends on 2)

The method of claim 2, wherein the reaction of the compound of formula (II) with the compound of formula (III) comprises the following steps:
placing the compound of formula (II) and the compound of formula (III), in a molar ratio of 1:1 to 1:1.3, in a reactor;
adding an organic solvent and a catalyst under nitrogen atmosphere to obtain a reaction mixture;
heating the reaction mixture at 50-85° C. for 1-4 hours;
concentrating the reaction mixture under reduced pressured to give a crude product; and
purifying the crude product on a silica gel column with petroleum ether and ethyl acetate as an eluent to obtain the compound of formula (I).

### Claim 4 (depends on 3)

The method of claim 3, wherein the organic solvent is toluene, ethyl acetate, or acetonitrile.

### Claim 5 (depends on 3)

The method of claim 3, wherein the catalyst is EDC.

### Claim 6 (depends on 3)

The method of claim 3, wherein the molar ratio of the compound of formula (II) and the compound of formula (III) is 1:1.1.

### Claim 7 (depends on 3)

The method of claim 3, wherein the reaction mixture is heated at 75° C.

### Claim 8 (depends on 3)

The method of claim 3, wherein the reaction mixture is heated for 4 hours.

### Claim 9 (depends on 3)

The method of claim 3, wherein the eluent is ethyl acetate:petroleum ether=3:10.

### Claim 10 (depends on 2)

The method of claim 2, wherein the reaction of the compound of formula (II) with the compound of formula (III) comprises the following steps:
placing the compound of formula (II), a catalyst, and an ionic liquid in a reactor under nitrogen atmosphere, the catalyst being 12-molybdosilicic acid hydrate (H6Mo12O41Si);
adding the compound of formula (III) to the reactor to form a reaction mixture;
heating the reaction mixture at 25-50° C. for 5-10 hours;
placing the reaction mixture in a separating funnel to separate a crude product;
purifying the crude product by recrystallization in methanol to obtain the compound of formula (I); and
recycling the ionic liquid.

### Claim 11 (depends on 10)

The method of claim 10, wherein the ionic liquid is 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]).

### Claim 12 (depends on 10)

The method of claim 10, wherein the compound of formula (II) and the compound (III) have a molar ratio of 1:1 to 1:1.3.

### Claim 13 (depends on 12)

The method of claim 12, wherein the molar ratio of the compound of formula (II) and the compound of formula (III) is 1:1.1.

### Claim 14 (depends on 10)

The method of claim 10, wherein the reaction mixture is heated at 25° C.

### Claim 15 (depends on 10)

The method of claim 10, wherein the reaction mixture is heated for 8 hours.