Methyl iodide → 8-Chloro-5-fluoro-4-methoxy-2-(trifluoromethyl)quinoline
Reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:17])=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:8]=[C:7]2[OH:16].[C:18]([O-])([O-])=O.[K+].[K+].IC>CC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:17])=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([F:13])([F:14])[F:15])[CH:8]=[C:7]2[O:16][CH3:18]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 8-Chloro-5-fluoro-2-(trifluoromethyl)quinolin-4-ol (Step 1, 3.54 g, 13.3 mmol, 1 eq.) in acetone (75 mL) was added anhydrous K2CO3 (3.88 g, 28.0 mmol, 2.1 eq.), followed by iodomethane (1.8 mL, 28.9 mmol, 2.17 eq.). The resulting mixture was stirred at reflux for 1.5 hours. An additional aliquot of iodomethane (1.8 mL, 28.9 mmol, 2.17 eq.) was added and reflux was continued for an additional 1 hour. The reaction was cooled to room temperature, poured onto ice and extracted with ethyl acetate. The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated on a rotary evaporator to give 3.72 g (100% yield) of the desired product as a yellow solid, which was used in subsequent reactions without further purification. An analytical sample was prepared by recrystallization from hexane/ethyl acetate; MP=198-200° C.; MS (ES) m/z (relative intensity): 280 (M+H)+ (100).
Workup
- temperatureat reflux for 1.5 hours
- temperaturereflux
- additionpoured onto ice
- extractionextracted with ethyl acetate
- dry with materialThe combined organic layers were dried over anhydrous MgSO4
- filtrationfiltered
- concentrationconcentrated on a rotary evaporator
Sources & evidence
- ORD record
- ord-4c0483d08e8845c5811d284469afa269
- Source dataset
- uspto-grants-2010_03
- Patent number
- US07671056B2
Reaction notes
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