Ammonia → 2-Chlorobicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile

Temperature

-78 °C

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).

1. customA dried 2 L 3-neck flask was fitted with a card-ice condenser
2. customsealed under nitrogen
3. customcondensed into the flask from a cylinder until approximately required volume
4. additionwas added over a 5 minute period
5. temperatureat reflux for 4 h
6. customThe ammonia was evaporated
7. additionwater was added to the solid residue
8. extractionthe products were extracted with dichloromethane (×3)
9. washThe combined organics were washed with dilute hydrochloric acid (5%)
10. dry with materialThe organics were dried with sodium sulfate
11. concentrationconcentrated

ORD record

ord-60ba7ebb745a4415931047ecf6f4efcb

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08729274B2