Scalable Synthesis of the Key Fexuprazan Intermediate and Investigation of a Reaction Mechanism.
ACS Omega
; 9(36): 37942-37952, 2024 Sep 10.
Article
em En
| MEDLINE
| ID: mdl-39281948
ABSTRACT
A three-step method for the synthesis of methyl 5-(2,4-difluorophenyl)-4-methoxy-1H-pyrrole-3-carboxylate 1, a key intermediate of fexuprazan, is reported in this paper. Using low-priced sodium p-tolylsulfinate as the starting material, compound 28 was obtained with a 96.8% yield in the first step by optimizing the experimental parameters with a Box-Behnken experimental design. Subsequently, isonitrile compound 29 was obtained by dehydration. Finally, impurities 31 and 32 in the last step of the reaction were identified and converted into target product 1 by a one-pot method, which significantly improves the utilization of atoms. Key intermediate 1 was obtained via a three-step process with a yield of 68-70% and purity that exceeded 99%. In addition, the mechanism of the cyclization reaction was proposed. This method has potential for industrial production because the raw materials are inexpensive, the procedure is simple, and a high yield is obtained.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
ACS Omega
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Estados Unidos