tert-Butanol → [4-(4-Benzyloxycarbonylamino-2-fluorophenoxy)pyridin-2-yl]carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

4-(4-Benzyloxycarbonylamino-2-fluorophenoxy)pyridine-2-carboxylic acid (500 mg) was dissolved in tert-butyl alcohol (5 ml), and triethylamine (0.457 ml) and diphenylphosphoryl azide (0.310 ml) were added thereto under a nitrogen atmosphere at room temperature, followed by stirring for 1.5 hr. The reaction mixture was heated up to 30° C. and stirred for 1 hr and at 40° C. for 45 min. The reaction mixture was heated up to 50° C. and stirred for 30 min, then heated up to 60° C. and stirred for 30 min. The reaction mixture was heated up to 70° C. and stirred for 30 min and at 80° C. for 30 min. The reaction mixture was heated up to 90° C. and stirred for 1.5 hr, then allowed to cool down to room temperature and stirred for 15 hr. The reaction mixture was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (30 ml). The organic layer was washed with water (30 ml) and brine (30 ml) in this order and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, the resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=3:2). Fractions containing the target compound were concentrated under reduced pressure to give a residue, which was suspended in diethyl ether (3 ml) and hexane (3 ml). The solid was collected by filtration and dried under aeration to provide the titled compound as a pale yellow solid (277 mg, 46.6%).

Provenance & Evidence