Methane → HCID 22716499, compound

Participants

Reaction Conditions

Reaction Steps

Equip a 12-L reaction flask with a cooling bath, air stirrer, and thermometer probe and charge with KOH (288.6 g, 5.143 moles) and water (6.04 L) to form a solution that exotherms to about 31° C. Allow the solution to cool to about 28° C., and charge the mixture with 4-chloro-2-thiophene carbonitrile (671.3 g, 4.675 moles) (a small amount of solids are undissolved). Add EtOH (675 mL), at which time a gradual exotherm occurs and continues over 1-1.5 h to about 38° C. Stir the reaction at ambient temperature overnight. Filter the reaction mixture under vacuum, wash with water, and dry to give crude product. Dissolve the solids in EtOAc (10.0 L), treat with Na2SO4 and activated charcoal for 1-2 h, then filter and wash with EtOAc. Concentrate the filtrate on a rotary evaporator at 45° C. until solids begin to precipitate out. Release the vacuum and increase the temperature to 60-65° C. to redissolve the solids. With stirring at 60° C., add heptane (3.5 L) slowly to precipitate solids. Stir for 15-20 min at 60° C., then cool the mixture to 30-40° C. and filter. Wash the solids with heptane (2×0.75 L), and dry to give the title compound as a white solid (235.4 g, 31%). Obtain a second crop (67.8 g, 9%) from the filtrate.

Provenance & Evidence