2-Chloro-6-methoxyquinoline

General procedure: Ina flask (50 mL) equipped with a magnetic stirrer bar and balloon, a mixture of triphenylphosphine (1191mg, 4.54 mmol) and trichloroisocyanuric acid (360 mg, 1.55 mmol) was heated under an argonatmosphere. During the heating process, triphenylphosphine melted, and trichloroisocyanuric acidvigorously reacted at 130-140 °C to form a dark brown oil, followed by further heating for 10 min.1-Methylquinolin-2(1H)-one (242 mg, 1.50 mmol) was added to the mixture followed by heating at130-140 °C for 3 h. Then, the reaction mixture was dissolved in CH2Cl2 and basified with triethylaminefollowed by silica gel column chromatography using hexane-EtOAc (6:1) as an eluate. The product2-chloroquinoline (204 mg, 82percent) was obtained.A solution of 6- methoxyquinolin-2-ol (400 mg, 2.29 mmol) in POCIA solution of 6- methoxyquinolin-2-ol (400 mg, 2.29 mmol) in POCIStep 1a A suspension of [6-METHOXY-1 H-QUINOLIN-2-ONE] of Step B (5.136 g, 29.2 [MMOL)] in toluene (100 mL) is treated with phosphorous oxychloride 913.8 mL) and heated at [95C] under nitrogen for 2 hours. The crude mixture is poured into ice water and basified with 50% aqueous sodium hydroxide. The solution is extracted with ethyl acetate, the extracts are dried over anhydrous magnesium sulfate and evaporated to dryness. The residue is pre-absorbed on silica gel Merck-60 and flash chromatographed using a gradient of ethyl acetate (10-20%) in hexane to provide the title compound (5.25 g) as a white crystalline solid, m. p. [105-107C.] MS [(+) ES, m/z] : 194.04 [M+H] +Step 1 A solution of 1.7 g of 6-methoxy-2(1H)-quinolone (10 mmoles) in 25 mL POCl3 was refluxed for 2 hours. The reagent was removed under reduced pressure and the resulting gum dissolved in CH2Cl2. The solution was washed with aqueous NaHCO3 to remove remaining acid, dried over MgSO4, and then evaporated to afford Phenylboronic acid (7.2 g, 58 mmol) and 2-Chloro-6-methoxy-quinoline (2.00 g, 10.3 mmol), (4-fluorophenyl)boronic acid (1.88 g, 13.4 mmol) and sodium carbonate (5.47 g, 51.6 mmol) were stirred and mixed.A mixed solvent of 1, 4-dioxane (80 mL) and water (20 mL) was added, and the mixture was stirred at room temperature for 10 minutes.Tetrakis(triphenylphosphine)palladium (612 mg, 0.529 mmol) was added, followed by heating to 100 C for reflux for 16 hours.The reaction was cooled to room temperature, suction filtered through Celite, ethyl acetate (100 mL) to wash the filter cake, The filtrate was washed with saturated ammonium chloride solution (50mL), dried over anhydrous sodium sulfate, filtered and concentratedThe resulting residue was purified by silica gel column chromatography [ethyl acetate / petroleum ether (v / v) = 1/20] was purified, To give the title compound 3b (1.88g, 69% yield) as a yellow solid.

Molecular Weight:193.63
XLogP3:2.7
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:193.0294416
Monoisotopic Mass:193.0294416
Topological Polar Surface Area:22.1
Heavy Atom Count:13
Complexity:176
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes