Diethyl (ethoxymethylene)malonate → Diethyl 2-((thiophen-3-ylamino)methylene)malonate

Participants

Reaction Steps

A mixture of methyl 3-aminothiophene-2-carboxylate 1 (5.0 g, 32 mmol, 1.0 eq), N-methyl piperazine (6.5 g, 64 mmol, 2.0 eq) and NMP (30 mL) was heated to reflux for 16 hours. After the decarboxylation was complete, the reaction mixture was allowed to cool to room temperature and diethyl 2-(ethoxymethylene)-malonate (7.0 g, 32 mmol, 2.0 eq) was added. The reaction mixture was heated to reflux for 4 h. The product was purified using SiO2 column chromatography (Hex/EtOAc; 100:0 to 80:20%) to obtain a light yellow powder, 5.0 g (31%). LC/MS (10-99% CH3CN/0.05% TFA gradient over 5 min): m/z 270.2, retention time 1.52 minutes. 1H NMR (DMSO-d6) δ: 10.80 (d, 1.0H, J=13.87 Hz, NH), 8.30 (d, 1.0H, J=13.94 Hz), 7.60 (dd, 1.0H, J=3.0 Hz, J′=2.0 Hz), 7.40 (dd, 1.0H, J=1.5 Hz, J′=3.13 Hz), 7.28 (dd, 1.0H, J=1.5 Hz, J′=5.2 Hz), 4.20 (q, 2H, J=7.0 Hz), 4.10 (q, 2H, J=7.0 Hz), 1.30 (m, 6H).

Provenance & Evidence