Triethylamine → Benzyl[4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-(4-benzyloxycarbonylamino-3-fluorophenyl)pyridine-2-carboxylic acid (2.85 g) in N-methylpyrrolidone (30 ml) were added triethylamine (2.59 ml) and 2-(trimethylsilyl)ethanol (1.28 ml), and then diphenylphosphoryl azide (2.59 ml) was added thereto, followed by stirring under a nitrogen atmosphere at room temperature for 1 hr and at 90° C. for 2 hrs. The reaction mixture was cooled down to room temperature and partitioned between ethyl acetate (100 ml) and a saturated aqueous solution of sodium hydrogencarbonate (100 ml). The organic layer was washed with brine. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; heptane:ethyl acetate=1:1 to 1:2, ethyl acetate, then ethyl acetate:methanol=20:1 to 10:1). Fractions containing the two respective target compounds were concentrated respectively to provide 2-(trimethylsilyl)ethyl [4-(4-benzyloxycarbonylamino-3-fluorophenoxy)pyridin-2-yl]carbamate (Production Example 119-2: 747 mg, 20.2%) as a yellow solid, and benzyl [4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamate (Production Example 119-1: 618 mg, 23.5%) as a brown solid.

Provenance & Evidence