4-METHOXY-6-CHLOROQUINOLINE synthesis

Yield:676262-10-5 63%

Reaction Conditions:

in methanol; for 17 h;Heating / reflux;

Steps:

46 Example 46 ; Cis-N-(1-Benzoyl-6-chloro-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl)-N-phenyl-acetamide

R1: phenyl, R2: CH3, R3: phenyl, R4: CH3, R5: H, R6: Cl, R7: H, R8: H. To a solution of 4,6-dichloroquinoline (4g) in methanol (50ml) was added 1.1 eq (1.1g) of sodium methoxyde. The mixture was heated under reflux for 17 hours. After cooling, the reaction mixture was evaporated under reduce pressure, dissolved in dichloromethane (80ml) and washed with water (80ml). The aqueous layer was extracted by 80ml of dichloromethane. The organic layers were combined and dried by sodium sulfate. The solvent was evaporated to give a brown oil which was chromatographed in silicagel using CH2Cl2 and CH2Cl2/MeOH 99/1 and then 98/2. The fractions containing 4-methoxy-6-chloro-quinoline (3a) were combined and evaporated to give a brown solid (2.5 g; yield = 63%).1H NMR [(CD3)2SO]: ? 8.8 (m, 1H), 8.10 (m, 1H), 7.98 (m, 1H), 7.75 (m, 1H), 7.10 (m, 1H), 4.05 (s, 1H). MS positive ESI: m/z (m+H)+= 193 (75%), 195 (25%) HPLC: rT: 4.97, 100% purity

References:

EP1413306,2004,A1 Location in patent:Page 42