3-(2,6-dichlorophenyl)propanenitrile

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A dried 2 L 3-neck flask was fitted with a card-ice condenser, sealed under nitrogen and cooled to −78° C. Ammonia gas was condensed into the flask from a cylinder until approximately required volume was present (˜300 mL). Commercial sodium amide (800 mmol, 31.2 g) was added to the ammonia at −78° C. and after stirring for 10 minutes 3-(2,6-dichlorophenyl)propanenitrile (200 mmol, 40 g) was added over a 5 minute period. The mixture was allowed to warm such that the resultant mixture was stirred at reflux for 4 h before being neutralised with solid ammonium nitrate (800 mmol, 64.0 g) and allowed to stand overnight under a flow of nitrogen. The ammonia was evaporated and water was added to the solid residue and the products were extracted with dichloromethane (×3). The combined organics were washed with dilute hydrochloric acid (5%), followed by water. The organics were dried with sodium sulfate and concentrated to afford crude 3-chloro-1,2-dihydrocyclobutabenzene-1-carbonitrile as a brown residue (98% yield, 32 g). A dried 2 L 3-neck flask was fitted with a card-ice condenser sealed under nitrogen condensed into the flask from a cylinder until approximately required volume was added over a 5 minute period at reflux for 4 h The ammonia was evaporated water was added to the solid residue the products were extracted with dichloromethane (×3) The combined organics were washed with dilute hydrochloric acid (5%) The organics were dried with sodium sulfate concentrated

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Cyano-3-(2,6-dichlorophenyl)propanoic acid (447 mmol, 109 g) was dissolved in DMA (179 ml) and heated for 2 hours at 150° C. After cooling, the reaction mixture was poured into water and extracted with ether. The organic layer was washed with a saturated solution of sodium hydrogen carbonate and then with a saturated solution of sodium chloride. The organic phase was dried over sodium sulfate and concentrated under reduced pressure to afford 3-(2,6-dichlorophenyl)propanenitrile (94% yield, 83.8 g). After cooling extracted with ether The organic layer was washed with a saturated solution of sodium hydrogen carbonate The organic phase was dried over sodium sulfate concentrated under reduced pressure

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Cyano-3-(2,6-dichlorophenyl)propanoic acid (447 mmol, 109 g) was dissolved in DMA (179 ml) and heated for 2 hours at 150° C. After cooling, the reaction mixture was poured into water and extracted with ether. The organic layer was washed with a saturated solution of sodium hydrogen carbonate and then with a saturated solution of sodium chloride. The organic phase was dried over sodium sulfate and concentrated under reduced pressure to afford 3-(2,6-dichlorophenyl)propanenitrile (94% yield, 83.8 g). After cooling extracted with ether The organic layer was washed with a saturated solution of sodium hydrogen carbonate The organic phase was dried over sodium sulfate concentrated under reduced pressure

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A dried 2 L 3-neck flask was fitted with a card-ice condenser, sealed under nitrogen and cooled to −78° C. Ammonia gas was condensed into the flask from a cylinder until approximately required volume was present (˜300 mL). Commercial sodium amide (800 mmol, 31.2 g) was added to the ammonia at −78° C. and after stirring for 10 minutes 3-(2,6-dichlorophenyl)propanenitrile (200 mmol, 40 g) was added over a 5 minute period. The mixture was allowed to warm such that the resultant mixture was stirred at reflux for 4 h before being neutralised with solid ammonium nitrate (800 mmol, 64.0 g) and allowed to stand overnight under a flow of nitrogen. The ammonia was evaporated and water was added to the solid residue and the products were extracted with dichloromethane (×3). The combined organics were washed with dilute hydrochloric acid (5%), followed by water. The organics were dried with sodium sulfate and concentrated to afford crude 3-chloro-1,2-dihydrocyclobutabenzene-1-carbonitrile as a brown residue (98% yield, 32 g). A dried 2 L 3-neck flask was fitted with a card-ice condenser sealed under nitrogen condensed into the flask from a cylinder until approximately required volume was added over a 5 minute period at reflux for 4 h The ammonia was evaporated water was added to the solid residue the products were extracted with dichloromethane (×3) The combined organics were washed with dilute hydrochloric acid (5%) The organics were dried with sodium sulfate concentrated

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Cyano-3-(2,6-dichlorophenyl)propanoic acid (447 mmol, 109 g) was dissolved in DMA (179 ml) and heated for 2 hours at 150° C. After cooling, the reaction mixture was poured into water and extracted with ether. The organic layer was washed with a saturated solution of sodium hydrogen carbonate and then with a saturated solution of sodium chloride. The organic phase was dried over sodium sulfate and concentrated under reduced pressure to afford 3-(2,6-dichlorophenyl)propanenitrile (94% yield, 83.8 g). After cooling extracted with ether The organic layer was washed with a saturated solution of sodium hydrogen carbonate The organic phase was dried over sodium sulfate concentrated under reduced pressure