Malonic Acid → 6-Bromo-4-hydroxy-7-methoxyquinolin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

To a mixture of 4-bromo-3-methoxyaniline (10 g, 49.5 mmol) and malonic acid (5.15 g, 49.5 mmol) was added POCl3 (5.07 ml, 54.4 mmol) with thorough mixing, and it was then heated to 105° C. After 5 minutes, the reaction began to bubble vigorously, and eventually formed a hard foam and heating was continued for 1 hour. After cooling, water (200 mL) was added, and the mixture was stirred for 30 minutes. The solid was filtered off and washed with water. To the solid was added 2N NaOH (300 mL) and stirring was continued overnight. The remaining solid was filtered off, and EtOH (5 mL) was then added to the filtrate and the basic layer acidified with concentrated HCl to pH 2. The resulting solid was then filtered off, washed with water. The solid was then transferred to a flask and the remaining water was removed by azeotroping with EtOH (200 mL×2). The solid was then further dried under high vacuum for 15 h to yield 8.75 g of the title compound as an off-white solid. LRMS ESI+ (M+H)+ Calcd 270.2 Found 272.2.

Provenance & Evidence