6-Quinolinecarboxylic acid, ethyl ester

A solution of 6-quinolinecarboxylic acid (9.50 g, 54.9 mmol) and 2 ml of concentrated sulfuric acid in ethanol (250 ml) was refluxed for 8 h. The solvent was evaporated and the residue was taken up in water. After adjustment of the pH to 8 by the addition of potassium hydroxide the product was collected by filtration and dried in vacuum. Yield 9.85 g (89percent) of ethyl 6-quinolinecarboxylate as a pale brown solid. M.p.: 66-67° C., TLC (CH2Cl2/MeOH/AcOH 9:0.5:0.1): Rf 0.52 [0346] A solution of ethyl 6-quinolinecarboxylate (9.80 g, 48.7 mmol) was acidified to pH 2 by the addition of 1N aqueous HCl. After addition of 20percent Pd-Mohr catalyst (1.96 g) the solution was hydrogenated at 60° C. under 3 bar of hydrogen pressure for 17 h. The reaction mixture was filtered through celite. The filtrate was evaporated and the residue was taken up in ethyl acetate and water. The pH was adjusted to 16 by the additon of 1 N aqueous potassium hydroxide. The phases were separated and the organic phase was washed with brine, dried over Na2SO4 and evaporated. Yield 8.72 g (87percent) of ethyl 1, 2, 3, 4-tetrahydro-6-quinolinecarboxylate as a pale brown solid. M.p.: 68-70° C., GC-MS: [M+]=205.To a solution of quinoline-6-carboxylic acid (2.8 g, 16 mmol) in ethanol (100 mL) was added concentrated sulfuric acid (2 mL). The reaction was heated to reflux overnight. The solvent was evaporated to give a brown residue that was taken up in ethyl acetate (150 mL). The mixture was washed with water (2.x.30 mL), saturated aqueous sodium bicarbonate (2.x.30 mL), and brine (2.x.30 mL). The organic layer was dried over sodium sulphate, filtered, and concentrated to an oil. Purification by flash column chromatography gave the title compound (2.0 g, 81percent) as a brown solid.Example 66: Synthesis of 6-f3-(2.4-dimethoχybenzylidene)-3A5, 6- tetrahydropyridin-2-yl)quinoline hydrochloride.; The preparation of 6-(3-(2, 4-dimethoxybenzylidene)-3, 4, 5, 6- tetrahydropyridin-2-yl)quinoline hydrochloride is described below.; A. Step 1: Preparation of Intermediate 14; Intermediate 14 was prepared as described in EP 0381375 Bl, page 21. 6- quinolinecarboxylic acid (12.2 g, 70.4 mmol) was suspended into ethanol (70 mL) in a reaction vessel. Concentrated sulfuric acid (12 mL) was added, the reaction vessel was sealed and the reaction was heated to 80General procedure: Au/AlAccurately weigh 0.005mmol (l. Lmg) of the transition metal, add 10mL has been put into the magnetic stirrer Young's reaction tube, The oxygen reaction was carried out in the Young's reaction tube, and the reaction was carried out under oxygen conditions. The syringe was applied to the Young's reaction tubeA solution of 0.04 mmol of co-catalyst I, 0.08 mmol of co-catalyst II, 0.2 mmol of 4-carboxylate and 1 ml of l-3'-propylene glycol, the above-mentioned Young's reaction tube was placed on a magnetic stirrer and stirred at 150 ° C for 12 h. After the reaction was completed, The pH of the solution was neutral, and the reaction solution was post-treated to obtain pure product of ethyl 6-formate quinoline in a yield of 45percent.

Molecular Weight:201.22
XLogP3:2.6
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:201.078978594
Monoisotopic Mass:201.078978594
Topological Polar Surface Area:39.2
Heavy Atom Count:15
Complexity:230
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes