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 minutes. The organic layer was separated, washed with brine, dried over anhydrous Na2SO4 and solvent evaporated to an oil which was azeotroped once with PhMe (50 mL). The oil was dissolved in chlorobenzene (50 mL) and 4A molecular sieves (5 g) added to the stirred solution. After 10 minutes, 1-chloroethylchloroformate (5.6 mL, 51 mmol) was added dropwise over 5 minutes. The reaction mixture was then heated to 90° C. for 2 hours, cooled to RT and filtered. The solids were washed with chlorobenzene (5 mL) and MeOH (40 mL). The filtrate was heated to 70° C. for 1 hour, allowed to cool and stirred at RT 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 PhMe (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 minutes
9. temperaturecooled to RT
10. filtrationfiltered
11. washThe solids were washed with chlorobenzene (5 mL) and MeOH (40 mL)
12. temperatureThe filtrate was heated to 70° C. for 1 hour
13. temperatureto cool
14. stirringstirred at RT overnight
15. filtrationThe solids were filtered
16. washwashed with chlorobenzene (2 mL) and hexane
17. customdried

ORD record

ord-350afa1927ad4482ae00e267e9bcd4af

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08377873B2