反应详情

Ketoprofen (1.11 mmol) (manufactured by Tokyo Kasei Kogyo) was dissolved in dichloromethane (3 ml), and triethylamine (1.11 mmol) and dichloromethane solution (2 ml) of dimethylphosphinothioyl chloride (Mpt-Cl) (1.11 mmol) were added thereto in this order, followed by stirring for 25 minutes. Triethylamine (0.36 mmol) was further added thereto, followed by stirring for 20 minutes. The reaction solution was ice-cooled, and triethylamine (1.11 mmol), DMAP (0.19 mmol) and the Boc-serinol obtained in Reference Example 2 (0.50 mmol) were added thereto in this order, followed by stirring overnight by returning to room temperature. The reaction solution was again ice-cooled, and 25% aqueous ammonia (2 ml) and dioxane (10 ml) were added thereto in this order, followed by stirring for 20 minutes. The reaction solution was concentrated to 5 ml, and ethyl acetate was added thereto. Separation by washing with water, 5% aqueous citric acid solution, 5% aqueous sodium hydrogen carbonate solution and saturated brine consecutively was carried out, and after dehydration drying with sodium sulfate the solvent was evaporated under reduced pressure. The precipitate was purified by silica gel column chromatography (hexane:ethyl acetate=2:1, 0.5% triethylamine) to give the titled compound (287.3 mg, yield 87%). The structure was identified by 1H-NMR (CDCl3).

1. stirringby stirring for 20 minutes
2. temperaturecooled
3. additionwere added
4. stirringby stirring overnight
5. customby returning to room temperature
6. temperaturecooled
7. stirringby stirring for 20 minutes
8. concentrationThe reaction solution was concentrated to 5 ml, and ethyl acetate
9. additionwas added
10. customSeparation
11. washby washing with water, 5% aqueous citric acid solution, 5% aqueous sodium hydrogen carbonate solution and saturated brine
12. dry with materialafter dehydration drying with sodium sulfate the solvent
13. customwas evaporated under reduced pressure
14. customThe precipitate was purified by silica gel column chromatography (hexane:ethyl acetate=2:1, 0.5% triethylamine)