3,5-Dimethylbenzenethiol → 6-Methoxyquinolin-3-amine

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3-Hydroxy-6-methoxyquinoline is not, a known compound, and the common methods for synthesizing quinolines are not readily applicable to 3-hydroxy substituents. p-Anisidine hydrochloride was treated with sodium nitromalonaldehyde to give the enamine 13. Heating the enamine 13 in a mixture of acetic acid sulfolane gave 3-nitro-6-methoxyquinoline 14 (30%). The yield of 14 could be improved to 48%, by heating p-anisidine hydrochloride and the enamine 13 in acetic acid in the presence of a catalylic amount of 3,5dimethylthiophenol. Reduction of 14 using stannous chloride gave 3-amino-6methoxyquinoline 15 (86%). Standard diazotization conditions and hydrolysis gave the phenol 16 (95%). Treatment of 16 with t-butyldimethylsilyl chloride/imidazole/in dimethylformamide gave 17 (91%) (FIG. 6).

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