ChemicalBook CAS DataBase List 4-Chloro-7-methoxyquinoline

4-Chloro-7-methoxyquinoline synthesis

8synthesis methods

Product Name:4-Chloro-7-methoxyquinoline
CAS Number:68500-37-8
Molecular formula:C10H8ClNO
Molecular Weight:193.63

190516-85-9

68500-37-8

1. 3-Methoxyaniline (1.23 g) and 5-methoxymethylene-2,2-dimethyl-[1,3]dioxane-4,6-dione (1.90 g) were dissolved in 2-propanol (40 ml), and the reaction was stirred at 70 °C for 1 hour. After completion of the reaction, the solvent was removed by distillation under reduced pressure and the residue was washed with ether to afford 5-[(3-methoxyphenylamino)-methylene]-2,2-dimethyl-[1,3]dioxane-4,6-dione (1.22 g, 44% yield). 2. 5-[(3-methoxyphenylamino)-methylene]-2,2-dimethyl-[1,3]dioxane-4,6-dione (1.22 g) was suspended in diphenyl ether (15 ml) with biphenyl (5.1 g) and reacted with stirring at 220 °C for 1.5 hrs. The reaction mixture was purified by column chromatography in methanol-chloroform system to afford 7-methoxy-1H-quinolin-4-one (394 mg, 51% yield). 3. 7-Methoxy-1H-quinolin-4-one (394 mg) was suspended in diisopropylethylamine (3 ml), phosphorus trichloride (1 ml) was added, and the reaction was stirred at 100 °C for 1 hour. After completion of the reaction, water was added under cooling in an ice bath, the aqueous layer was neutralized with aqueous sodium bicarbonate and the organic layer was extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried with anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure and the residue was purified by column chromatography in acetone-chloroform system to afford 4-chloro-7-methoxyquinoline (312 mg, 72% yield).

82121-05-9 Synthesis

82121-05-9
186 suppliers
$58.00/5g

68500-37-8
203 suppliers
$18.00/250mg

Yield:68500-37-8 88%

Reaction Conditions:

with trichlorophosphate for 3 h;Heating;

Steps:

5.4 4-Chloro-7-methoxyquinoline (7)

A mixture of 7-methoxyquinolin-4(1H)-one 6 (10mmol) and phosphorous oxychloride (30mL) was heated for 3h. Most of phosphorous oxychloride was removed by evaporation under reduced pressure, and the residue was poured into ice water. Then, the mixture was made alkaline with ammonium hydroxide; the precipitate formed was collected by filtration, washed well with water and dried in a vacuum; and compound 7 was obtained as white solid (1.7g, 88%). ESI-MS m/z 194 [M+H]⁺. ¹H NMR (300MHz, CDCl₃): δ 8.67 (1H, d, J= 4.8Hz, ArH), 8.09 (1H, d, J= 9.0Hz, ArH), 7.42 (1H, d, J= 2.4Hz, ArH), 7.33 (1H, d, J= 4.8Hz, ArH), 7.28 (1H, dd, J=9.0Hz, J=2.4Hz, ArH), 3.97 (3H, s, CH₃). ¹³C NMR (75MHz, CDCl₃) δ 161.3, 151.0, 150.2, 142.4, 125.3, 121.7, 120.8, 119.3, 107.7, 55.9.

References:

Li, Shangze;Hu, Lihua;Li, Jianru;Zhu, Jiongchang;Zeng, Feng;Huang, Qiuhua;Qiu, Liqin;Du, Runlei;Cao, Rihui [European Journal of Medicinal Chemistry,2019,vol. 162,p. 666 - 678]

82121-05-9 Synthesis

82121-05-9
186 suppliers
$58.00/5g

68500-37-8
203 suppliers
$18.00/250mg

References