Acetic Acid → Tert-butyl [3-(cyclopropylamino)phenyl]carbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl(3-aminophenyl)carbamate (6.91 g, 33.2 mmol) in methanol (30 mL) were added acetic acid (5.69 mL, 99.5 mmol) and [(1-ethoxycyclopropyl)oxy](trimethyl)silane (7.98 mL, 39.8 mmol), and the mixture was stirred at 60° C. for 4 hr. The reaction mixture was concentrated under reduced pressure. A solution of the obtained residue in tetrahydrofuran (20 mL) was added dropwise to a suspension of sodium tetrahydroborate (2.51 g, 66.4 mmol) and boron trifluoride diethyl ether complex (8.33 mL, 66.4 mmol) in tetrahydrofuran (30 mL) (the suspension was stirred in advance at room temperature for 1 hr) at 0° C. over 30 min, and the mixture was stirred at room temperature for 2.5 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution (100 mL), and the mixture was extracted with ethyl acetate (2×50 mL). The combined organic layer was washed with saturated brine (20 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=95/5→90/10), and the fractions containing the object product were concentrated under reduced pressure to give the title compound (4.87 g, 59%) as a colorless solid.

Provenance & Evidence