Acetic Acid → 2-Tert-butyl 4-ethyl 3,5-dimethyl-1h-pyrrole-2,4-dicarboxylate

Participants

Reaction Conditions

Reaction Steps

Into a 10-L four necked round-bottomed flask equipped with a mechanical stirrer, a thermometer pocket and an air condenser, were charged tertiary butyl acetoacetate (1.0 Kg; 6.3 mole) and acetic acid (3.0 Lt). The solution was cooled to 0-5° C. and a previously dissolved solution of sodium nitrite (0.436 Kg; 6.3 mole) in 640 mL DM water into an addition funnel and added to the flask at a rate that the temperature does not exceed 5° C. After the addition, the solution was maintained for 90 minutes at 0-5° C. and slowly brought the reaction mixture to room temperature (25-30° C.) over a period of 4 hours. At this temperature, ethyl acetoacetate (0.824 Kg; 6.3 mole) was charged at once followed by Zinc powder (0.94 Kg; 14.4 mole) in ten equal lots below 70° C. After addition of zinc powder, the reaction mixture was maintained for 1-2 hours at 65-70° C. The resulting solution was cooled to 60° C. and quenched in a carboy containing 25.0 Lt DM water under stirring. The product was extracted with ethyl acetate and separated using separating funnel. The organic layer was then clarified by treating the product solution with activated charcoal followed by filtration through hyflow. The solvent was then recovered by distillation under diminished pressure and the traces were removed by the addition of methanol (500 ml) to the distillation flask and continued distillation under diminished pressure. The resulting product was triturated in 95% aqueous methanol (1.5 L) at 0-5° C. for 2 hours to get a crystalline product of formula-II.

Provenance & Evidence