Large Scale One-Pot Synthesis of 4-Substituted-1H-Pyrrole-3-Carboxylates

Significance

Reported is a multikilogram synthesis of 4-substituted 1H-pyrrole-3-carboxylates by the Horner-Wadsworth-Emmons reaction of aldehydes with triethylphosphonoacetate followed by treatment with tosylmethylisocyanide (TosMIC). Several improvements to well-known procedures (t-PentONa and toluene instead t-BuONa and THF-MeCN) allowed both reactions to be performed as a one-pot process and the isolation of clean (>95% HPLC) products without extra purification in fair to good yield. Using the procedure, from 2.8 kg (18 mol) of 1-naphthylcarbaldehyde 2.96 kg (62%) of ethyl 4-(1-naphthyl)-1H-pyrrole-carboxaldehyde were obtained.