Bicarbonate Ion → 2-Benzyl-4-bromo-2,3-dihydro-1H-isoindole
Reaction equation
C(=O)(O)[O-].[Br:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12]Br)[C:7]=1[CH2:14]Br.[CH2:16]([NH2:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CC#N>[CH2:16]([N:23]1[CH2:14][C:7]2[C:8](=[CH:9][CH:10]=[CH:11][C:6]=2[Br:5])[CH2:12]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
Postassium bicarbonate (204 g, 2.04 mol) was suspended in CH3CN (12 L), and the mixture was heated to 80° C. Solutions of 1-bromo-2,3-bis(bromomethyl)benzene (280 g, 0.82 mol in 500 mL CH3CN) and benzylamine (87.5 g, 0.82 mol in 500 mL CH3CN) were added concurrently via addition funnels over 1 hour. The reaction mixture was then stirred at 77° C. for 16 hours. The contents of the reaction flask were cooled and filtered; the solvent was removed by evaporation; and the mixture was partitioned between 1M K2CO3 and EtOAc. The organic phases were washed with brine, dried with anhydrous Na2SO4, filtered, and evaporated. Flash column chromatography (gradient elution: heptane to 10% EtOAc in heptane) gave the title compound as a pale oil. 1H NMR (CDCl3) δ (ppm) 7.41-7.39 (m, 2H), 7.37-7.34 (m, 2H), 7.32-7.27 (m, 2H), 7.10-7.03 (m, 2H), 4.02 (s, 2H), 3.97 (s, 2H), 3.91 (s, 2H). LRMS (ESI) m/z 289 [(M+H)+; calcd for C15H15BrN: 289].
Workup
- temperatureThe contents of the reaction flask were cooled
- filtrationfiltered
- customthe solvent was removed by evaporation
- customand the mixture was partitioned between 1M K2CO3 and EtOAc
- washThe organic phases were washed with brine
- dry with materialdried with anhydrous Na2SO4
- filtrationfiltered
- customevaporated
- washFlash column chromatography (gradient elution: heptane to 10% EtOAc in heptane)
Sources & evidence
- ORD record
- ord-4415e659e13c4ccaa17b6573c1359790
- Source dataset
- uspto-grants-2013_02
- Patent number
- US08377874B2
Reaction notes
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