Ethyl cyanoacetate → Ethyl 4-cyanooxane-4-carboxylate

Participants

Reaction Steps

To a suspension of NaH (22.11 g, 552.1 mmol) in DMF (350 mL) is added ethyl cyanoacetate (23.5 mL, 195 mmol) at 0° C. over 25 min. The reaction mixture is warmed to room temperature for 2 h and it is cooled down to 0° C. again. A solution of 1-chloro-2-(2-chloroethoxy)ethane (31.1 mL, 265.4 mmol) in DMF (50 mL) is added and the reaction mixture is warmed to room temperature for 1 h. Then the reaction mixture is heated at 90° C. for 16 h before the reaction is quenched with ice cold water (180 mL). The mixture is extracted with EtOAc (2×200 mL) and the organic layers are combined, dried (Na2SO4) and concentrated. The crude compound is purified by fractional distillation under high vacuum to afford the title compound (10 g, 25%) as a colorless oil.

Provenance & Evidence