反应详情

Methyl aminoacetate hydrochloride (292 mg, 2.33 mmol) was suspended in a solvent mixture of N,N-dimethylformamide (4 ml) and triethylamine (1 ml); phenyl N-(4-(1-(ethylamino)carbonyl-1H-5-indolyloxy)-2-pyridyl)-N-(phenoxycarbonyl)carbamate (250 mg, 0.466 mmol, Production example 55-1) was added thereto; and the reaction mixture was stirred at room temperature for 2 days. The reaction mixture was partitioned between ethyl acetate and water; and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was dissolved in a solvent mixture of tetrahydrofuran (2 ml) and methanol (1 ml); and 4N aqueous solution of sodium hydroxide was added thereto while stirred at room temperature; and the reaction mixture was stirred for 1.5 hour at room temperature. After 1N hydrochloric acid was added, extraction was performed with ethyl acetate-tetrahydrofuran, washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained crystals were suspended in diethyl ether, filtered off, washed with dimethyl ether, and dried under aeration to yield the title compound as colorless crystals (149 mg, 0.375 mmol, 80.5%).

1. customThe reaction mixture was partitioned between ethyl acetate and water
2. washand the organic layer was washed with brine
3. dry with materialdried over anhydrous sodium sulfate
4. concentrationconcentrated under reduced pressure
5. dissolutionThe obtained residue was dissolved in a solvent mixture of tetrahydrofuran (2 ml) and methanol (1 ml)
6. additionand 4N aqueous solution of sodium hydroxide was added
7. stirringwhile stirred at room temperature
8. stirringand the reaction mixture was stirred for 1.5 hour at room temperature
9. additionAfter 1N hydrochloric acid was added
10. extractionextraction
11. washwashed with brine
12. dry with materialdried over anhydrous sodium sulfate
13. concentrationconcentrated under reduced pressure
14. filtrationfiltered off
15. washwashed with dimethyl ether
16. customdried under aeration