Pyrrole Chemistry. An Improved Synthesis of Ethyl Pyrrole-2-Carboxylate Esters from Diethyl Aminomalonate
Paine, J.B. and David Dolphin
J. Org. Chem.,
Pyrrole-2-carboxylates I (R = Me, Et; R1 = H, Me, Et, Pr, CH2CO2Me, CH2CH2CO2Me; R2 = Me, Et, Pr, CH2CH2CO2Et), versatile precursors for the total synthesis of both synthetic model and naturally occurring tetrapyrroles and porphyrins, were prepd. in greatly improved yields by the addition of RCOCHR1COR2 and H2NCH(CO2)Et)2 to AcOH. The method is suitable for both small- and large-scale synthesis and has proved far more reliable than the in situ Zn reduction of HON=C(CO2Et)2. Yields range from 60-70% for the dominant product isomer from unsymmetric diketones to 75-90% for the single product derived from symmetric diketones. RCOCHR1COR2 were prepared by treating RCOCHR1 with (R2CO)2O in the presence of BF3.