Example 1: Synthesis of tert-butyl {3-[(hydroxyamino)carbonyl]quinolin-6-yl}carbamate (Compound 1-21, Int-2)
Step 1: Synthesis of methyl 6-bromoquinoline-3-carboxylate (Intermediate 1)
[00161] To a solution of 6-bromoquinoline-3-carboxylic acid (3 g, 11.9 mmol) in methanol (55 mL) was slowly added concentrated sulfuric acid (0.32 mL, 6 mmol). The reaction mixture was stirred and refluxed at 85 °C for 96 hours. Upon completion of the reaction, the mixture was cooled to room temperature and the pH was adjusted to 7 by slow addition of saturated sodium bicarbonate solution.During neutralization, methyl 6-bromoquinoline-3-carboxylate precipitated as a solid, which was collected by filtration (Intermediate 1, 2.77 g, 97% yield).
Product Characterization:
LC-MS (FA) ES+ m/z: 266 [M+H]+.
1H NMR (400 MHz, DMSO-d6) δ ppm: 9.33 (d, J = 2.1 Hz, 1H), 9.01 (d, J = 2.1 Hz, 1H), 8.53 (t, J = 1.3 Hz, 1H), 8.07-8.01 (m, 2H), 3.95 (s, 3H).
