Hydrochloric Acid → HCID 20279332, compound

Participants

Reaction Conditions

Reaction Steps

Potassium cyanide (5.85 g.) was added to a solution of ethyl 2-[1-(4-bromo-2-fluorobenzyl)-2-oxo-3-indolinidyl]-2-cyanoacetate (D) (35.0 g.) in methanol (80 ml.). The mixture was stirred for 2 hours, cooled to 0° C. and then saturated with dry hydrogen chloride at 0°-10° C. The solution obtained was left overnight at ambient temperature, heated at 50°-55° C. for 1 hour and then under reflux for 4 hours. The cooled reaction solution deposited a solid which was collected; washed with water, air dried and then heated under reflux in acetic acid (85 ml.) for 12 hours. This mixture was cooled and the solid residue removed by filtration. The filtrate was evaporated, residual acetic acid being removed by azeotropic evaporation with toluene (3×150 ml.). The oily residue obtained was dissolved in ethyl acetate (100 ml.) and absorbed onto chromatographic silica gel (30 g.) by evaporation of the solvent. The residue was added to a column of silica gel (300 g.) made up in toluene. Elution with an increasing concentration of ethyl acetate in toluene (up to 25% v/v) and combination and evaporation of those fractions containing the major component (relative flow value 0.6), gave 1'-(4-bromo-2-flurobenzyl)-4-cyano-spiro[pyrrolidine-3,3'-indoline]-2,2',5-trione (5.5 g.), m.p. 208°-210° C., after recrystallisation from ethyl acetate/petrol 60-80.

Provenance & Evidence