反应详情

温度

90 °C

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.

1. temperatureThe reaction mixture was cooled down to room temperature
2. custompartitioned between ethyl acetate (100 ml)
3. washThe organic layer was washed with brine
4. customThe solvent was evaporated
5. customto give a residue, which
6. customwas then purified by silica gel column chromatography (eluent
7. additionFractions containing the two respective target compounds
8. concentrationwere concentrated respectively