2-Bromobenzyl cyanide → 1-(1,3-dioxolan-2-ylidene)-1H-indene-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

Ethyl 3-ethoxyacrylate (36.9 kg, 255.0 moles), 2-bromophenyl acetonitrile (50 kg, 255. 1 moles), and tetrahydrofuran (57 L) were combined in reactor 1 and the resultant solution was stirred at 25° C. until needed (4 hours.). Palladium II acetate (1.3 kg, 5.7 moles), tricyclohexylphosphine (1.9 kg, 6.7 moles), and tetrahydrofuran (148 L) were combined in reactor 2 and the resultant mixture was stirred for 30 minutes at 25° C. The mixture was then cooled to 5° C. and sodium t-butoxide (61.3 kg, 637.7 moles ) was added to reactor 2 at 5° C. The resulting mixture was warmed to 15° C. and stirred for 15 minutes and then cooled back to 5° C. The contents in reactor 1 were then slowly charged to reactor 2 over 2 hours. at 10° C. and then the contents in reactor 2 were stirred for 15 minutes at 10° C. Reactor 2 was then slowly heated to 60° C. at a rate of 8 to 2° C. per hour (5 hours.) and then held at 60° C. for 4 hours. The reaction was then cooled to 5° C. and ethylene glycol was added at 5° C. The Tetrahydrofuran in the reaction was then distilled off. The reaction was again cooled to 10° C. and sulfuric acid (88.4 kg) added over 1.5 hours at 10° C. The reaction was heated to 40° C. at a rate of 8 to 12° C. per hour (3 hours) and held at 40° C. for 8 hours. The reaction was cooled to 10° C. and ammonium hydroxide (44.8 kg) and water (201 L) were added. The slurry was warmed to 20° C. and granulated for 2 hours. The solid was filtered and washed with water (61 L). The crude solid was recharged to the reactor and water (220 L) added. The slurry was granulated at 20° C. for 4.5 hours and then filtered. The filter cake was washed with water (61 L) and the product dried at 55° C.

Provenance & Evidence