6-hydroxyquinoline-3-carboxylic acid synthesis

Yield: 91%

Reaction Conditions:

with hydrogen bromide;acetic acid in water at 140; for 1 h;Microwave irradiation;

Steps:

5.11.1
Example 11: N-hydroxy-6-phenoxyquinoline-3-carboxamide Compound 1-12 Step 1: 6-hydi*oxyquinoline-3-carboxylic acid Intermediate-15 [00183] 6-Methoxyquinoline-3-carbox lic acid (0.75 g, 3.69 mmol) was placed in a 20 mL microwave vial fitted with a stirbar. The solid was suspended in acetic acid (7 mL) and hydrobrorrric acid (48 % in water, 3.5 mL) was added. The vial was capped and the suspension was carefully heated under microwave irradiation at 140 °C for 1 h. After reaction, the vial was thoroughly cooled to room temperature and very carefully vented with an 18 g needle in a fume hood prior to opening. The solids were collected by filtration and washed with ethyl acetate to afford the title product as a solid (0.678 g, 91 %). LC-MS: (FA) ES+ 190; ^.H NMR (400 MHz, d₆-DMSO) δ ppm 10.68 (br s, 1 H), 9.26 (d, J = 1.9 Hz, 1 H), 9.14 (d, J = 1.3 Hz, 1 H), 8.08 (d, J = 9.1 Hz, 1 H), 7,62 (dd, J = 9.1, 2.7 Hz, 1 H), 7.52 (d, J = 2.7 Hz, 1 H).

References:

MILLENNIUM PHARMACEUTICALS, INC.;GOULD, Alexandra, E.;HARRISON, Sean, J. WO2011/146591, 2011, A1 Location in patent:Page/Page column 69