反应详情

Ethyl 4-aminobutyrate hydrochloride (1.0 g, 6.0 mmol) was suspended in N,N-dimethylformamide (6.7 ml), 5N aqueous solution of sodium hydroxide (1.2 ml, 6.0 mmol) was added and the reaction mixture was stirred at room temperature. Phenyl N-(4-(1-(methylamino)carbonyl-1H-indol-5-yloxy)pyridin-2-yl)-N-(phenoxycarbonyl)carbamate (700 mg, 1.3 mmol, Production example 5-2) was added thereto and the reaction mixture was stirred at room temperature for 1.2 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Fuji Silysia BW-300, ethyl acetate) to yield a pale yellow oil. This oil was dissolved in tetrahydrofuran (6.0 ml) and methanol (3.0 ml); 4N lithium hydroxide (1.1 ml) was added thereto at room temperature; and the reaction mixture was stirred at room temperature for 3.5 hours. Moreover, 1N hydrochloric acid (4.4 ml) and water (2 ml) were added thereto while stirred at room temperature; and this was subjected to extraction with ethyl acetate, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. After the precipitated crystals were suspended in diethyl ether:hexane=1:1, the crystals were filtered off, washed with diethyl ether, and dried under aeration to yield the title compound (411 mg, 1.0 mmol, 75%) as colorless crystals.

1. stirringthe reaction mixture was stirred at room temperature for 1.2 hours
2. customThe reaction mixture was partitioned between ethyl acetate and water
3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. customThe residue was purified by silica gel column chromatography (Fuji Silysia BW-300, ethyl acetate)
6. customto yield a pale yellow oil
7. customat room temperature
8. stirringand the reaction mixture was stirred at room temperature for 3.5 hours
9. stirringwhile stirred at room temperature
10. extractionand this was subjected to extraction with ethyl acetate
11. washwashed with brine
12. dry with materialdried over anhydrous magnesium sulfate
13. concentrationconcentrated under reduced pressure
14. filtrationhexane=1:1, the crystals were filtered off
15. washwashed with diethyl ether
16. customdried under aeration