Sodium Hydroxide → 4-bromo-2,3-dihydro-1H-isoindole

Temperature

90 °C

To a solution of 2-benzyl-4-bromoisoindoline hydrochloride (11 g, 30.96 mmol) in 200 mL EtOAc was added 1M NaOH (100 mL) and the mixture stirred for 30 min. The organic layer was separated, washed with brine, dried over anhydrous Na2SO4 and solvent evaporated to an oil which was azeotroped once with toluene (50 mL). The oil was dissolved in chlorobenzene (50 mL) and 4A molecular sieves (5 g) added to the stirred solution. After 10 min, 1-chloroethylchloroformate (5.6 mL, 51 mmol) was added dropwise over 5 min. The reaction mixture was then heated to 90° C. for 2 h, cooled to room temperature and filtered. The solids were washed with chlorobenzene (5 mL) and methanol (40 mL). The filtrate was heated to 70° C. for 1 h., allowed to cool and stirred at room temperature overnight. The solids were filtered, washed with chlorobenzene (2 mL) and hexane and dried to give 6.84 g of title compound. LRMS (ESI) m/z 198.1 [(M+H)+; calcd for C8H9BrN: 198.0].

1. customThe organic layer was separated
2. washwashed with brine
3. dry with materialdried over anhydrous Na2SO4 and solvent
4. customevaporated to an oil which
5. customwas azeotroped once with toluene (50 mL)
6. dissolutionThe oil was dissolved in chlorobenzene (50 mL)
7. addition4A molecular sieves (5 g) added to the stirred solution
8. waitAfter 10 min
9. temperaturecooled to room temperature
10. filtrationfiltered
11. washThe solids were washed with chlorobenzene (5 mL) and methanol (40 mL)
12. temperatureThe filtrate was heated to 70° C. for 1 h.
13. temperatureto cool
14. stirringstirred at room temperature overnight
15. filtrationThe solids were filtered
16. washwashed with chlorobenzene (2 mL) and hexane
17. customdried

ORD record

ord-bd6314cabaa0480eb1ede6396ce7d88f

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07470664B2