1. Efficient route to 3-methoxymethylquinolines – A precursor of 5-methoxymethylquinolinic acid
- Author
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Jason Yang, Julie Holland, Ramiah Murugan, Gregory F. Hillstrom, Paul E. Krieger, Eric F. V. Scriven, and Calvin Joel R
- Subjects
Organic Chemistry ,Quinoline ,chemistry.chemical_element ,Sodium methoxide ,Chloride ,Medicinal chemistry ,Catalysis ,lcsh:QD241-441 ,chemistry.chemical_compound ,lcsh:Organic chemistry ,chemistry ,medicine ,Organic chemistry ,Dimethylformamide ,Methanol ,Sodium carbonate ,Palladium ,medicine.drug - Abstract
An efficient process for preparing 3-methoxymethylquinolines, commencing from substituted anilines and 3-chloropropionyl chloride, has been developed. Reaction of substituted anilines with 3-chloropropionyl chloride in the presence of sodium carbonate produced 3-chloro-N- (substituted phenyl)propionamide, which was treated with dimethylformamide and phosphorus oxychloride (Vilsmeier Reaction) at 85 o C to give 2-chloro-3-chloromethyl substituted quinoline. Selective methoxylation of this dichloro intermediate with sodium methoxide in methanol at 45 o C gave 2-chloro-3-methoxymethyl substituted quinoline, which was dehalogenated by palladium catalyzed hydrodehalogenation to give 3-methoxymethyl substituted quinoline in nearly quantitative yield.
- Published
- 2002
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