cis-1,2,3,6-Tetrahydrophthalimide → cis-2,3,3a,4,7,7a-Hexahydro-1h-isoindole

Temperature

60 °C

A suspension of lithium aluminum hydride (21.4 g, 0.562 mol) in THF (700 mL) at room temperature was treated with cis-1,2,3,6-tetrahydrophthalimide (Aldrich; 37 g, 0.245 mol) in small portions. The reaction mixture was stirred at 60° C. overnight then cooled to room temperature and quenched carefully by the sequential addition of water (22 mL), THF (22 mL), 15% aqueous KOH (22 mL), and water (80 mL). The mixture was diluted with diethyl ether (100 mL), stirred at room temperature for 1 hour, and then filtered (methylene chloride wash). The filtrate was concentrated under reduced pressure to provide the title compound as an oil (26.1 g). 1H NMR (CDCl3, 300 MHz) δ 1.76–2.02 (m, 2H), 2.10–2.33 (m, 3H), 2.34–2.56 (m, 2H), 2.61–2.79 (m, 2H), 2.87–3.17 (m, 2H), 5.53–6.03 (m, 2H); MS (DCI/NH3) m/z 124 (M+H)+.

1. temperaturethen cooled to room temperature
2. customquenched carefully by the sequential addition of water (22 mL), THF (22 mL), 15% aqueous KOH (22 mL), and water (80 mL)
3. additionThe mixture was diluted with diethyl ether (100 mL)
4. stirringstirred at room temperature for 1 hour
5. filtrationfiltered
6. wash(methylene chloride wash)
7. concentrationThe filtrate was concentrated under reduced pressure

ORD record

ord-2ba0ec14a5b3474b830853cd83ec00dd

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07135484B2