One-step continuous flow synthesis of highly substituted pyrrole-3-carboxylic acid derivatives via in situ hydrolysis of tert-butyl esters

Org Lett. 2010 Nov 19;12(22):5182-5. doi: 10.1021/ol102216x. Epub 2010 Oct 21.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / chemistry
  • Combinatorial Chemistry Techniques
  • Esters
  • Hydrolysis
  • Molecular Structure
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Stereoisomerism

Substances

  • Amides
  • Carboxylic Acids
  • Esters
  • Pyrroles
  • pyrrole-3-carboxylic acid