Pyridine → 7-(benzyloxy)-N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-nitroquinolin-4-amine

Participants

Reaction Conditions

Reaction Steps

A 2-necked 2-liter round bottom flask was charged with 2-{[7-(benzyloxy)-3-nitroquinolin-4-yl]amino}ethanol (95.0 g, 0.28 mol) and pyridine (400 mL). The suspension was heated to 65° C. To the resulting homogenous solution was added in one portion tert-butyldimethylsilyl chloride (46.4 g, 0.31 mol, 1.1 eq) and 4-(N,N-dimethylamino)pyridine (3.42 g, 0.028 mol, 0.1 eq). The reaction temperature rose to 87° C., was slowly cooled to 65° C., and was maintained overnight at this temperature. The reaction was determined to be incomplete. Additional tert-butyldimethylsilyl chloride (20 g, 0.13 mol, 0.5 eq) was added in one portion and the reaction temperature was increased to 70° C. for 8 hours. The reaction was still not complete. Additional tert-butyldimethylsilyl chloride (21.5 g, 0.14 mol, 0.5 eq) was added in one portion and the reaction was maintained at 70° C. overnight. The reaction was now complete. The reaction mixture was poured into a 2-liter flask, followed by an ethyl acetate rinse, and set aside over the weekend. A precipitate, determined to be pyridine hydrochloride, formed and was removed by filtration. The reaction mixture was then concentrated under reduced pressure to a brown/yellow solid. The solid was slurried in ethyl acetate and collected by filtration; this was repeated three times. The combined filtrates were washed with water and then concentrated to approximately one-third of the original volume until solid began to precipitate. The mixture was diluted with hexane (700 mL) and stirred for an additional hour. A light brown solid was collected by vacuum filtration and dried overnight to provide 102.6 g of 7-(benzyloxy)-N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-nitroquinolin-4-amine, which was used without further purification in the next step.

Provenance & Evidence