# US 2021/0276986 A1 · Method for preparing beta-lactam derivative

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- Number: US 2021/0276986 A1
- Document ID: US20210276986A1
- Status: Published application
- Kind: A1
- Application number: 17/256,088
- Filed: 2019-09-04
- Published: 2021-09-09
- Earliest claimed: 2018-12-06
- Assignees: Soochow University
- Applicants: Soochow University
- Inventors: Runsheng ZENG; Peng SHI; Yingsheng ZHAO
- Web page: https://patentgrep.com/patent/US20210276986A1

## CPC

- C07D 409/14: containing three or more hetero rings
- B01J 31/1805: {the ligands containing nitrogen}
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/10: linked by a carbon chain containing aromatic rings
- C07D 405/14: containing three or more hetero rings
- B01J 31/006: {comprising organic radicals, e.g. TEMPO}
- B01J 2231/70: Oxidation reactions, e.g. epoxidation, (di)hydroxylation, dehydrogenation and analogues
- B01J 2531/16: Copper
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS

## Abstract

The present invention relates to a method for preparing a β-lactam derivative, wherein a substituted N-quinoline-3-butenamide derivative is used as a substrate to react with a toluene derivative or a heterocyclic derivative at 90-150° C. in the presence of DTBP and a copper salt catalyst, to prepare a β-lactam derivative. According to the method of the present invention, a variety of β-lactam derivatives can be obtained with a high yield. The reaction of the present invention has mild reaction conditions, and simple reaction operation and post-treatment process, and is suitable for large-scale production.

## Claims

### Claim 1

A method for preparing a β-lactam derivative, comprising the steps of:
reacting a substituted N-quinoline-3-butenamide derivative of Formula (1) and a toluene derivative of Formula (2) at 90-150° C. in the presence of di-tert-butyl peroxide and a copper salt catalyst, to give a β-lactam derivative of Formula (4), where the reaction route is as follows:
or reacting a substituted N-quinoline-3-butenamide derivative of Formula (1) and a heterocyclic derivative of Formula (3) at 90-150° C. in the presence of di-tert-butyl peroxide and a copper salt catalyst, to give a β-lactam derivative of Formula (5), where the reaction route is as follows:
wherein in Formulas (1)-(5), Y is an oxygen or sulfur atom; and
R2 and R3 are hydrogen, and R1 is hydrogen, methyl, halo or trifluoromethyl;
or R1 and R2 are hydrogen, and R3 is C1-C6 alkyl or benzyl;
or R1 and R3 are hydrogen, and R2 is C1-C6 alkyl, allyl, benzyl, phenylethyl, cyclopropylmethyl, or cyclobutylmethyl.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the copper salt catalyst is selected from the group consisting of cuprous bromide, copper acetate, cuprous chloride, tetrakis(acetonitrile)copper hexafluorophosphate, copper trifluoromethanesulfonate, copper oxide, copper bromide and any combination thereof.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the molar ratio of the substituted N-quinoline-3-butenamide derivative: di-tert-butyl peroxide:copper salt catalyst=1:1-3:0.05-0.2.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the copper salt catalyst is tetrakis(acetonitrile)copper hexafluorophosphate.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the molar ratio of the substituted N-quinoline-3-butenamide derivative: di-tert-butyl peroxide:copper salt catalyst=1:3:0.05-0.2.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the reaction temperature is 130 to 150° C.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the reaction system also comprises, in addition to the toluene derivative of Formula (2) or the heterocyclic derivative of Formula (3), an additional organic solvent.

### Claim 8 (depends on 7)

The method according to claim 7, wherein the organic solvent is selected from the group consisting of acetonitrile, tetrahydrofuran, N,N-dimethylformamide, isopropanol and any combination thereof.