Chloride → 2-Methylquinoline
Reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O/C=C/C(Cl)=O)C.OC1C=C[C:24]2[C:19](=[CH:20][CH:21]=CC=2)N=1.[Cl-].C(=O)/C=C/C>P(Cl)(Cl)(Cl)=O>[CH3:21][C:20]1[CH:19]=[CH:24][C:7]2[C:2](=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:1]=1Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
Aniline 22 may be acylated with (E)-3-ethoxyacryloyl chloride and treatment of the resulting amide with sulfuric acid leads to hydroxyquinoline 29, which can be converted to the corresponding chloride 30 by heating in phosphorus oxychloride. Condensation of aniline 24 with crotonaldehyde in the presence of acid and an oxidant affords the 2-methylquinoline 31. The use of other aldehydes under similar conditions can lead to alternatively substituted quinolines. Oxidation of quinoline 31 with selenium dioxide can provide either aldehyde 32 or carboxylic acid 33, depending on the amount of oxidant used and the duration of the reaction. Reduction of aldehyde 32 with sodium borohydride provides the corresponding alcohol, and treatment of this with thionyl chloride may be used to give the chloride 34. Intermediates such as 30, 32, 33 and 34 may be converted to compounds of the present invention using a variety of known methodology. While the methodology shown in Scheme 6 is exemplified using aniline 22, it is understood that it may be applied to a variety of aniline substrates, such as those described herein, in order to provide various quinoline intermediates.
Sources & evidence
- ORD record
- ord-f95ea19160654e5a8a770b1fca8dff64
- Source dataset
- uspto-grants-2011_12
- Patent number
- US08071771B2
Reaction notes
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