6-Methoxy-3-nitroquinoline → 6-Methoxyquinolin-3-amine

Participants

Reaction Conditions

Reaction Steps

21.2 g (0.104 mole) of the nitroquinoline 14 was added portionwise to a 1.0 L beaker containing 320 mL conc. HCI at 50° C., with vigorous stirring. Then the heating bath was removed and 71.0 g of SnCl2 ·2H2O (0.312 mole, finely ground) was added portionwise over 2-3 min (the temperature of the mixture reached 80° C.). The mixture was stirred vigorously for 10 min, and diluted with water to 1.0 L. The pH was adjusted to 9 using 5M NaOH (900-950 mL) and the aqueous layer (2.0 L) was cooled to 4° C., and extracted with EtOAc (3×500 mL). The combined organic layers were washed with ice-cold water (200 mL), brine (400 mL) and dried over anhydrous MgSO4. Filtration and removal of the solvent in vacuo gave 17.6 g of crude 15. The crude product was vigorously stirred with 50 mL CHCl3 and the tan microcrystalline solid forming was filtered on a sintered glass funnel. The precipitate was washed with CHCl3 (2×25 mL) and then air dried. Removal of the last traces of solvent in vacuo gave 8.1 g of product. The washings were combined with the filtrate, concentrated by rotovap and placed in the freezer. Two more crops of 15 were thus obtained (3.8 and 2.3 g). The mother liquor concentrate was purified by column chromatography on silica gel (EtOAc -hexanes 1:1) and a further 1.3 g of product 15 was obtained (overall yield 15.5 g, 86%). A small amount of 4-chloro-6-methoxy-3-aminoquinoline (5%) was also obtained as a less polar byproduct.

Provenance & Evidence