反应详情

温度

10 °C

Pyridine (50 ml) was mixed with tetrahydrofuran (40 ml) and cooled to 10° C. A solution of phenyl chloroformate (4.83 g) in acetonitrile (50 ml) and a solution of 1-[4-(2-aminopyridin-4-yloxy)-2-fluorophenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester (10.00 g) in tetrahydrofuran (80 ml) were added dropwise to the tetrahydrofuran-pyridine solution over a period of 2 hours at 10° C. At this time, the amounts of the phenyl chloroformate-acetonitrile solution and the 1-[4-(2-aminopyridin-4-yloxy)-2-fluorophenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester/tetrahydrofuran solution added dropwise were adjusted to the constant rate so that each solution was added dropwise over a period of 2 hours. The crystals were precipitated while the solutions were added dropwise. After completing the dropwise addition, the completion of reaction was confirmed using an HPLC apparatus. Subsequently, a mixed solution of water (10 ml) and acetonitrile (50 ml) was added to the reaction mixture. The crystals were collected by filtration and washed with a mixed solution of tetrahydrofuran (15 ml)-acetonitrile (15 ml) and dried under reduced pressure to give the title compound (12.74 g). Apparent yield 98.0%, purity 94.6% (HPLC area percentage).

1. additionwas added dropwise over a period of 2 hours
2. customThe crystals were precipitated while the solutions
3. additionwere added dropwise
4. additionthe dropwise addition
5. customthe completion of reaction
6. filtrationThe crystals were collected by filtration
7. washwashed with a mixed solution of tetrahydrofuran (15 ml)-acetonitrile (15 ml)
8. customdried under reduced pressure