Methyl cyanoacetate → Methyl 1-cyanocyclopentane-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a 22 L flask equipped with a mechanical stirrer, thermometer and condenser containing a nitrogen inlet was added dry DMF (8 L) and methyl cyanoacetate (800 g, 8.07 mol). Stirring was started and K2CO3 (2.67 kg, 19.3 mol) and then 1,4-dibromobutane (1.74 kg, 8.07 mmol) were added. The exothermic reaction mixture (temperature increased to 75° C.) was stirred at room temperature for 16 h followed by heating at 60-75° C. for 3 h. Approximately 2.5 L of solvent were removed under reduced pressure and the residue was diluted with water (8 L). The resultant mixture was extracted with Et2O (2×2 L) and the combined organic phases were washed with 1 N aqueous HCl and brine. Drying (MgSO4), filtering and concentrating afforded an orange liquid. This material was distilled (fraction boiling at 80° C., 0.7 mm Hg collected) to provide methyl 1-cyanocyclopentanecarboxylate as a clear colorless liquid (953 g, 77% yield). 1H-NMR (400 MHz, CDCl3) δ 3.80 (s, 3 H), 2.29-2.22 (m, 4 H), 1.90-1.84 (m, 4 H); 13C NMR (100.6 MHz, CDCl3) δ 169.2, 119.9, 52.6, 46.6, 36.9, 24.3; EI-MS exact mass calcd for C8H11NO2 : 153.0790; found: 153.0785.

Provenance & Evidence