Dimethyl 3-oxoglutarate → methyl 2-(5-oxo-1-(2-phenylpropan-2-yl)-4,5-dihydro-1H-pyrazol-3-yl)acetate

tert-Butyl 2-(2-phenylpropan-2-yl)hydrazinecarboxylate (250 mg, 1.00 mmol) was dissolved in methylene chloride (2 mL), mixed with p-toluenesulfonic acid monohydrate (0.40 g, 2.1 mmol) and stirred at room temperature for 18 hours. The reaction solution was basified with saturated aqueous sodium hydrogen carbonate and separated. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in toluene (2.0 mL) and acetic acid (70 μL), mixed with dimethyl 1,3-acetonedicarboxylate (174 mg, 1.00 mmol) and stirred at 90° C. for 3 hours and at 105° C. for 3 hours. After completion of the reaction, the reaction solution was allowed to cool to room temperature and diluted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate and then with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by intermediate pressure silica gel column chromatography (silica gel12 g, ethyl acetate:hexane=1:9 to 3:7) to give 96.3 mg of the desired product as a white solid.

1. customseparated
2. washThe organic layer was washed with saturated aqueous sodium chloride
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationthe filtrate was concentrated under reduced pressure
6. dissolutionThe resulting residue was dissolved in toluene (2.0 mL)
7. stirringstirred at 90° C. for 3 hours and at 105° C. for 3 hours
8. customAfter completion of the reaction
9. temperatureto cool to room temperature
10. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate
11. dry with materialwith saturated aqueous sodium chloride, dried over anhydrous sodium sulfate
12. filtrationfiltered
13. concentrationthe filtrate was concentrated under reduced pressure
14. customThe resulting residue was purified by intermediate pressure silica gel column chromatography (silica gel12 g, ethyl acetate:hexane=1:9 to 3:7)

ORDレコード

ord-e1d33a0014ef49b0a544c1fb1f20cbf7

出典データセット

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08658686B2