Potassium Carbonate → 1-Chloro-4-ethoxyisoquinoline
Reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9](F)[CH:10]=2)[C:5]([OH:13])=[CH:4][N:3]=1.C([O-])([O-])=O.[K+].[K+].[CH:20]1(CBr)C[CH2:21]1>C(#N)C>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:13][CH2:20][CH3:21])=[CH:4][N:3]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 50 °C
Procedure
To a solution of 1-chloro-7-fluoro-4-hydroxyisoquinoline (1.0 g, 5.06 mmol) in acetonitrile (10 ml) was added K2CO3 (2 g, 15.18 mmol) followed by cyclopropylmethylbromide (1.36 g, 10.12 mmol) at room temperature. The reaction mixture was heated to 50° C. for 2 hr. Solvent was evaporated under reduced pressure and the residue was diluted with water and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure to get crude compound. The crude compound was purified by silica gel chromatography to get 1-chloro-4-ethoxyisoquinoline (0.7 g, 55%) as pale yellow solid. 1H NMR (400 MHz, CDCl3): δ ppm 8.38-8.34 (q, J=8 Hz, 1H), 7.89-7.86 (d, J=12 Hz, 1H), 7.81 (s, 1H), 7.65 (t, J=10 Hz, 1H), 4.11-4.09 (d, J=8 Hz, 2H), 1.43-1.37 (m, 1H), 0.72-0.67 (m, 2H), 0.46-0.39 (m, 2H); MS: MS m/z 252.0 (M++1).
Workup
- customSolvent was evaporated under reduced pressure
- additionthe residue was diluted with water
- extractionextracted with ethyl acetate
- dry with materialThe combined organic layer was dried over anhydrous Na2SO4
- customevaporated under reduced pressure
- customto get crude compound
- customThe crude compound was purified by silica gel chromatography
Sources & evidence
- ORD record
- ord-120dcf58922247a3b836d29c2aba88b7
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08957203B2
Reaction notes
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