One-step continuous flow synthesis of highly substituted pyrrole-3-carboxylic acid derivatives via in situ hydrolysis of tert-butyl esters.
The first one-step, continuous flow synthesis of pyrrole-3-carboxylic acids directly from tert-butyl acetoacetates, amines, and 2-bromoketones is reported. The HBr generated as a byproduct in the Hantzsch reaction was utilized in the flow method to hydrolyze the t-butyl esters in situ to provide the corresponding acids in a single microreactor. The protocol was used in the multistep synthesis of pyrrole-3-carboxamides, including two CB1 inverse agonists, directly from commercially available starting materials in a single continuous process.
Apoptosis and Cell Death Research Program & Conrad Prebys Center for Chemical Genomics, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, United States.
Ananda
A
Herath
Nicholas D P
ND
Cosford
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D004952:Esters; D006868:Hydrolysis; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000577:Amides; D002264:Carboxylic Acids; D004952:Esters; D011758:Pyrroles; C554881:pyrrole-3-carboxylic acid