Tetrahydrofuran → cis-2,3,3a,4,7,7a-Hexahydro-1h-isoindole

Temperature

60 °C

To a solution of 1 M LAH in THF (800 mL; 0.8 mole; 2.3 eq) at rt was added, portionwise, tetrahydrophthalimide (52.6 g; 0.348 mole; 1 eq). The reaction mixture was stirred at 60° C. for 16 hours, then cooled to RT and quenched carefully with sequential addition of 30 mL of water, 30 mL of THF, 15% aqueous KOH (30 mL), and water (100 mL). The mixture was diluted with 135 mL of ether, stirred at RT for 1 hour, and filtered through a pad of diatomaceous earth on a 600 mL fritted glass filter funnel, washing the pad with 400 mL of DCM. The filtrate was concentrated in vacuo to yield (3aR,7aS)-2,3,3a,4,7,7a-hexahydro-1H-isoindole as an oil, which was used directly in the next reaction as is.

1. temperaturecooled to RT
2. customquenched carefully with sequential addition of 30 mL of water, 30 mL of THF, 15% aqueous KOH (30 mL), and water (100 mL)
3. additionThe mixture was diluted with 135 mL of ether
4. stirringstirred at RT for 1 hour
5. filtrationfiltered through a pad of diatomaceous earth on a 600 mL fritted glass
6. filtrationfilter funnel
7. washwashing the pad with 400 mL of DCM
8. concentrationThe filtrate was concentrated in vacuo

ORD record

ord-38a7a8b073a74997ae17984c7f7d16be

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08481524B2