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.
Org Lett. 2010 Nov 19;12(22):5182-5. doi: 10.1021/ol102216x. Epub 2010 Oct 21.
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.
首次报道了通过叔丁基乙酰乙酸酯、胺和 2-溴代酮一步连续流合成吡咯-3-羧酸。在 Hantzsch 反应中生成的 HBr 副产物被用于流动方法原位水解叔丁酯，在单个微反应器中提供相应的酸。该方案用于多步合成吡咯-3-羧酰胺，包括两种 CB1 反向激动剂，直接从商业上可获得的起始原料在单个连续过程中进行。
