* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
A solution of 6- methoxyquinolin-2-ol (400 mg, 2.29 mmol) in POCI3 (5.0 mL) was refluxed for 2 hours. The solvent was removed under reduced pressure and the residue was dissolved in EtOAc (50 mL), the organic layer was washed with saturated NaHC03 (30 mL x2), dried over Na2S04, filtered and concentrated to give the crude product, which was purified by silica gel column (PE / EtOAc=10 / 1) to give 2-chloro-6-methoxyquinoline (380 mg, yield 86percent) as a solid. 1H NMR (CDC13 400 MHz): δ 7.92 (d, J = 8.4 Hz, 1H), 7.85 (d, J = 9.2 Hz, 1H), 7.32-7.25 (m, 2H), 7.00 (d, J = 2.4 Hz, 1H), 3.86 (s, 3H).
86%
for 2 h; Reflux
A solution of 6- methoxyquinolin-2-ol (400 mg, 2.29 mmol) in POCI3 (5.0 mL) was refluxed for 2 hours. The solvent was removed under reduced pressure and the residue was dissolved in EtOAc (50 mL), the organic layer was washed with saturated NaHCC>3 (30 mL x2), dried over Na2S04, filtered and concentrated to give the crude product, which was purified by silica gel column (PE / EtOAc=10 / 1) to give 2-chloro-6-methoxyquinoline (380 mg, yield 86percent) as a solid. *H NMR (CDC13 400 MHz): δ 7.92 (d, J = 8.4 Hz, 1H), 7.85 (d, J = 9.2 Hz, 1H), 7.32-7.25 (m, 2H), 7.00 (d, / = 2.4 Hz, 1H), 3.86 (s, 3H).
Reference:
[1] Patent: WO2012/48181, 2012, A1, . Location in patent: Page/Page column 74
[2] Patent: WO2012/83165, 2012, A1, . Location in patent: Page/Page column 91
[3] Ann. Inst. Pasteur, 1930, vol. 44, p. 719,736
4
[ 13676-00-1 ]
[ 19315-93-6 ]
Reference:
[1] Heterocyclic Communications, 2008, vol. 14, # 3, p. 183 - 186
[2] Journal of Medicinal Chemistry, 1986, vol. 29, # 10, p. 2024 - 2028
A solution of 6- methoxyquinolin-2-ol (400 mg, 2.29 mmol) in POCI3 (5.0 mL) was refluxed for 2 hours. The solvent was removed under reduced pressure and the residue was dissolved in EtOAc (50 mL), the organic layer was washed with saturated NaHC03 (30 mL x2), dried over Na2S04, filtered and concentrated to give the crude product, which was purified by silica gel column (PE / EtOAc=10 / 1) to give 2-chloro-6-methoxyquinoline (380 mg, yield 86%) as a solid. 1H NMR (CDC13 400 MHz): delta 7.92 (d, J = 8.4 Hz, 1H), 7.85 (d, J = 9.2 Hz, 1H), 7.32-7.25 (m, 2H), 7.00 (d, J = 2.4 Hz, 1H), 3.86 (s, 3H).
86%
With trichlorophosphate; for 2h;Reflux;
A solution of 6- methoxyquinolin-2-ol (400 mg, 2.29 mmol) in POCI3 (5.0 mL) was refluxed for 2 hours. The solvent was removed under reduced pressure and the residue was dissolved in EtOAc (50 mL), the organic layer was washed with saturated NaHCC>3 (30 mL x2), dried over Na2S04, filtered and concentrated to give the crude product, which was purified by silica gel column (PE / EtOAc=10 / 1) to give 2-chloro-6-methoxyquinoline (380 mg, yield 86%) as a solid. *H NMR (CDC13 400 MHz): delta 7.92 (d, J = 8.4 Hz, 1H), 7.85 (d, J = 9.2 Hz, 1H), 7.32-7.25 (m, 2H), 7.00 (d, / = 2.4 Hz, 1H), 3.86 (s, 3H).
A solution of 6- methoxyquinoline 1-oxide (300 mg, 1.71 mmol) in Ac20 (5.0 mL) was refluxed for 2 hours. The solvent was removed under reduced pressure. The residue was dissolved in EtOAc (50 mL), the organic layer was washed with brine (10 mL), dried over Na2S04, filtered and concentrated to give the crude product which was purified by silica gel column (PE / EtOAc=l / 2) to give 6-methoxyquinolin-2-ol (200 mg, yield 67%).
67%
With acetic anhydride; for 2h;Reflux;
A solution of 6- methoxyquinoline 1-oxide (300 mg, 1.71 mmol) in Ac20 (5.0 mL) was refluxed for 2 hours. The solvent was removed under reduced pressure. The residue was dissolved in EtOAc (50 mL), the organic layer was washed with brine (10 mL), dried over Na2S04, filtered and concentrated to give the crude product which was purified by silica gel column (PE / EtOAc=l / 2) to give 6-methoxyquinolin-2-ol (200 mg, yield 67%).
With zinc(II) oxide; In diethyl ether; for 2h;Irradiation;
Accurately weigh the reaction substrate 6-methoxyquinoline-N-oxide (175.1 mg, 1.0 mmol) and zinc oxide (3 mol%, 2.4 mg) into a quartz reactor, add 2.0 ml of ether, in air conditions After reacting for 2 hours under a xenon lamp irradiation, the ether was removed by a rotary evaporator, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1). product. The product was a white powdery solid in a yield of 95% (166.3 mg).
In acetic anhydride; at 75℃; for 18h;
The crude <strong>[6563-13-9]6-methoxyquinoline 1-oxide</strong> of Step A (70 [MMOL)] is suspended in acetic anhydride (70 mL) and heated at [75C] under nitrogen for 18 hours. The mixture is poured onto ice and carefully basified with ammonium hydroxide. The precipitate is collected, washed with hexane and dried. The solid is suspended in dichloromethane, filtered and dried to provide the title compound (5.136 g). Additional material (1.79 g) is obtained by flash chromatography of the mother liquors on silica gel [MARCK-60] using a gradient of methanol (1-5%) in hexane-ethyl acetate (1: [1).] MS [(+) ES, m/z]: 176.1 [M+H] +
With acetic anhydride; In tert-butyl alcohol; at 80℃; for 66h;
Acetic anhydride (0.94 mL, 10 mmol) was added to a solution of <strong>[6563-13-9]6-methoxyquinoline N-oxide</strong> (1.75 g, 10 mmol, see: Dimsdale, M. J. J. Het. Chem. 1979, 16, 1209) in tertiary butanol (10 mL). The resulting mixture was heated at 80 C for 18 h then additional acetic anhydride (0.94 mL, 10 mmol) was added. The mixture was heated at 80 C for an additional 2 days. The reaction mixture cooled to rt and was diluted with EtOAc and water. The organic phase was collected and washed with sat. NaHCO3, dried and concentrated to afford 6-methoxy-1H-quinolin-2-one (0.45 g). This material was converted to the title compound using the method described in Preparation 23.
With trichlorophosphate; In toluene; at 95℃; for 2h;
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] +
With trichlorophosphate; In dichloromethane; trichlorophosphate;
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 2-chloro-6-methoxy-quinoline as a solid.
With sodium persulfate; iron(III) chloride hexahydrate; In water; acetonitrile; at 80℃;
Compound I-2 (177 mg, 1 mmol), ferric trichloride hexahydrate (2.7 mg, 0.01 mmol) and sodium peroxodisulfate (286 mg, 1.2 mmol) were added to a reaction flask with a reflux condenser, and acetonitrile (5 mL) was added. ) And water (5 mL) and stir well at room temperature. The mixture was stirred with heating at 80 C for 2-3 hours until the reaction was completed. The reaction mixture was concentrated by heating to remove most of the acetonitrile, and then slowly cooled to room temperature, and a solid was gradually precipitated. The product was dried by filtration to obtain 154 mg of the product II-2 as an off-white solid, with a yield of 88%.