Synthesis 2024; 56(04): 577-584
DOI: 10.1055/a-2217-0996
special topic
Synthetic Development of Key Intermediates and Active Pharmaceutical Ingredients (APIs)

Efficient and Scalable Synthesis of 6,6-Dimethyl-3-oxabicyclo [3.1.0]hexan-2-one through Organocatalyzed Desymmetrization and Chemoselective Reduction

Guillaume Tintori
a   Minakem Recherche, 145 Chemin des Lilas, 59310 Beuvry-La-Forêt, France
,
Clément Jacob
a   Minakem Recherche, 145 Chemin des Lilas, 59310 Beuvry-La-Forêt, France
,
Christine Delsarte
a   Minakem Recherche, 145 Chemin des Lilas, 59310 Beuvry-La-Forêt, France
,
François Potié
a   Minakem Recherche, 145 Chemin des Lilas, 59310 Beuvry-La-Forêt, France
,
Laurence Grimaud
b   LBM, Département de Chimie, École Normale Supérieure, PSL University, Sorbonne Université, CNRS, 75005 Paris, France
,
Maxime Vitale
b   LBM, Département de Chimie, École Normale Supérieure, PSL University, Sorbonne Université, CNRS, 75005 Paris, France
,
a   Minakem Recherche, 145 Chemin des Lilas, 59310 Beuvry-La-Forêt, France
› Author Affiliations
This work was fully funded by Minakem.


This work is dedicated to Professor Aloïs Fürstner

Abstract

The development of a robust process to 6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one, a key intermediate toward several active compounds of interest, is described. A scalable organocatalyzed desymmetrization was first studied and the reaction proved to be compatible with standard dilution. A kinetic study was performed to elucidate substrate and catalyst concentration dependences. Next, a chemoselective reduction of the carboxylic acid was developed. The scalability was demonstrated on 100 g scale through a fully telescoped process.

Supporting Information



Publication History

Received: 13 October 2023

Accepted after revision: 23 November 2023

Accepted Manuscript online:
23 November 2023

Article published online:
02 January 2024

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