Hydrochloric Acid → 5-methoxy-2,3-dihydro-1H-isoindole

Temperature

0 °C

A stirred solution of 4-methoxyphthalimide (21.3 g, 0.12 mol) in anhydrous tetrahydrofuran (425 ml) at 0° C. was treated dropwise with a solution of borane in tetrahydrofuran (1M, 340 ml, 0.34 mol) and the resulting mixture was stirred and held at reflux for 16 hours. The mixture was cooled to 0° C., methanol (150 ml) was added dropwise followed by 5M hydrochloric acid (150 ml) and the mixture was stirred and held at reflux for 3 hours. Upon cooling to room temperature the organic solvent was removed in vacuo, the mixture was diluted with water (750 ml) and was extracted with dichloromethane (3×750 ml). The aqueous layer was basified to pH 12 or above by the addition of 5M sodium hydroxide, extracted with dichloromethane (3×750 ml) and the combined extracts were evaporated to dryness in vacuo to afford 5-methoxyisoindoline (8.34 g, 47%) as a brown oil. 1H NMR (DMSO-d6) 7.13 (1H, d), 6.84 (1H, d), 6.74 (1H, dd), 4.05 (2H, s), 4.01 (2H, s), 3.73 (3H, s). MS: [M+H]+ 150.

1. temperatureat reflux for 16 hours
2. stirringthe mixture was stirred
3. temperatureat reflux for 3 hours
4. temperatureUpon cooling to room temperature the organic solvent
5. customwas removed in vacuo
6. additionthe mixture was diluted with water (750 ml)
7. extractionwas extracted with dichloromethane (3×750 ml)
8. additionThe aqueous layer was basified to pH 12 or above by the addition of 5M sodium hydroxide
9. extractionextracted with dichloromethane (3×750 ml)
10. customthe combined extracts were evaporated to dryness in vacuo

ORD record

ord-abf498723d7e4cefad610f732205221b

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07754725B2