反应详情

To a solution of 4-(2-methyl-4-nitrophenoxy)pyridin-2-ylamine (1.00 g, 4.08 mmol) in tetrahydrofuran (50 ml) was added triethylamine (1.14 ml, 8.16 mmol), and then phenyl chloroformate (0.768 ml) was added dropwise thereto while stirring in an ice bath, followed by stirring for 1 hr. Phenyl chloroformate (0.252 ml) was further added thereto while stirring in an ice bath, followed by stirring for 30 min. The reaction mixture was concentrated under a reduced pressure to give a residue, to which N,N-dimethylformamide (18.9 ml) and morpholine (1.42 ml) were added, followed by stirring at room temperature for 5 hrs. The reaction mixture was partitioned between ethyl acetate:tetrahydrofuran=1:1 (150 ml) and water (100 ml). The aqueous layer was extracted with ethyl acetate:tetrahydrofuran=1:1. The combined organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; hexane:ethyl acetate=2:1 to 1:1, then ethyl acetate). The crude fraction was concentrated to give a residue, which was purified again by silica gel column chromatography (eluent; hexane:ethyl acetate=1:1, ethyl acetate, and then ethyl acetate:methanol=10:1) to provide the titled compound (772 mg, 52.8%) as a colorless solid.

1. stirringby stirring for 1 hr
2. stirringwhile stirring in an ice bath
3. stirringby stirring for 30 min
4. concentrationThe reaction mixture was concentrated under a reduced pressure
5. customto give a residue
6. stirringby stirring at room temperature for 5 hrs
7. customThe reaction mixture was partitioned between ethyl acetate
8. extractionThe aqueous layer was extracted with ethyl acetate
9. washThe combined organic layer was washed with brine
10. dry with materialdried over anhydrous sodium sulfate
11. customThe solvent was evaporated
12. customto give a residue, which
13. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent
14. concentrationThe crude fraction was concentrated
15. customto give a residue, which
16. customwas purified again by silica gel column chromatography (eluent