Potassium Hydroxide → 6-(Methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[4-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

Participants

Reaction Steps

Methyl 3-methyl-6-(methylsulfonyl)-2-[4-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.11 g, 2.62 mmol) was added to a flask and azeotroped with benzene to remove any residual water. NBS (0.513 g, 2.88 mmol) and diphenylperoxyanhydride (0.064 g, 0.262 mmol) were added, and the solids were suspended in carbon tetrachloride (42 mL). The solutions was heated to reflux for 24 hrs, cooled to room temperature, and concentrated to a minimal volume to afford a light yellow slurry. The slurry was redissolved in acetonitrile (42.0 mL), and 4-(4-piperidinyl)morpholine (0.669 g. 3.93 mmol) was added. The solution was stirred overnight, then concentrated to dryness. The residue was dissolved in 2N HCl and extracted with CH2Cl2. The phases were separated, and the organic phase was washed with HCl. The combined aqueous extracts were made basic with NaOH (2N) and extracted three times with CH2Cl2. The combined organic extracts were passed over a phase separator and concentrated to afford a yellow residue. The residue was dissolved in methanol (120 ml), water (21 ml) and KOH (1.471 g, 26.2 mmol), and the mixture was refluxed overnight. The reaction mixture was concentrated under reduced pressure to remove MeOH, additional water was added, and the mixture was stirred at room temperature for 1 h. The solid precipitate was collected by filtration to afford the desired product as an off white solid (1.1 g, 68%). MS (m/z) 578.2 (M+H+).

Provenance & Evidence