Hydrochloric Acid → 4-Chloro-2,3-dihydro-1H-isoindole

Temperature

80 °C

To solid 4-chloro-1H-isoindole-1,3(2H)-dione (4.0 g, 22.0 mmol) was added borane-THF complex (1 M/THF, 88.1 mL, 88.1 mmol) dropwise with stirring. When the addition was complete, the reaction mixture was heated to reflux (80° C.) and stirred for 6 h. The reaction mixture was then cooled to 0° C., methanol (2.8 mL, 88.1 mmol) was carefully added dropwise and the reaction mixture was warmed to room temperature. HCl (6 N) was added until the mixture was acidic and then the mixture was concentrated. The crude product was dissolved in 1 M HCl and extracted twice with ethyl ether and twice with dichloromethane. The pH of the aqueous layer was adjusted to pH=11 with solid NaOH and extracted three times with ethyl acetate. The combined ethyl acetate extracts were dried over Na2SO4, filtered and concentrated to give 4-chloroisoindoline (1.8 g, 53% yield). LRMS (ESI) m/z 154 [(M+H)+; calcd for C8H9ClN: 154].

1. additionWhen the addition
2. temperaturethe reaction mixture was heated
3. stirringstirred for 6 h
4. temperatureThe reaction mixture was then cooled to 0° C.
5. temperaturethe reaction mixture was warmed to room temperature
6. concentrationthe mixture was concentrated
7. dissolutionThe crude product was dissolved in 1 M HCl
8. extractionextracted twice with ethyl ether and twice with dichloromethane
9. extractionextracted three times with ethyl acetate
10. dry with materialThe combined ethyl acetate extracts were dried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated

ORD record

ord-03abb9b00284400fbc463bc7e693f964

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08216999B2