Cl.C([N:9]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][C:15]=2[Br:18])[CH2:10]1)C1C=CC=CC=1.[OH-].[Na+].ClC(OC(Cl)=O)C>CCOC(C)=O>[Br:18][C:15]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:16]=1[CH2:17][NH:9][CH2:10]2To 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].
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