Anisole → 1-Bromo-6,7-dimethoxyisoquinoline-4-carbonitrile
Reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9](=O)[NH:8][CH:7]=[C:6]2[C:16]#[N:17].P(Br)(Br)([Br:20])=O.C1(OC)C=CC=CC=1>>[Br:20][C:9]1[C:10]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[C:12]([O:13][CH3:14])[CH:11]=2)[C:6]([C:16]#[N:17])=[CH:7][N:8]=1Participants
Conditions
- Temperature
- 110 °C
Procedure
To a mixture of 6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carbonitrile. (3.5 g, 15.2 mmol) and phosphorus oxybromide (30 g, 105 mmol) was added anisole (3.2 mL, 30.4 mmol). The reaction mixture was heated at 110° C. for 1 h. The excess phosphorus oxybromide was removed in vacuo. The mixture was then neutralized to pH=7 by addition of saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted with dichloromethane (3×200 mL). The combined extracts were washed with saturated aqueous sodium chloride solution (100 mL), dried with anhydrous magnesium sulfate, filtered and concentrated in vacuo. The crude product was recrystallized from chloroform and diethyl ether to afford product 1-bromo-6,7-dimethoxy-isoquinoline-4-carbonitrile (1 g, 22.7% yield) as a white solid.
Workup
- customThe excess phosphorus oxybromide was removed in vacuo
- additionThe mixture was then neutralized to pH=7 by addition of saturated aqueous sodium bicarbonate solution
- extractionThe aqueous phase was extracted with dichloromethane (3×200 mL)
- washThe combined extracts were washed with saturated aqueous sodium chloride solution (100 mL)
- dry with materialdried with anhydrous magnesium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe crude product was recrystallized from chloroform and diethyl ether
Sources & evidence
- ORD record
- ord-e4962cf9ec014c8594764a8e446d7697
- Source dataset
- uspto-grants-2006_06
- Patent number
- US07067529B2
Reaction notes
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