反应详情

温度

100 °C

To a solution of the 4-methyl-1H-indazol-5-ol (500 mg, 1.83 mmol) obtained in Example 402 in toluene (8 ml) were added cis-2-(5-hydroxy-2,2-dimethylcyclohexyl)-1H-isoindole-1,3(2H)-dione (400 mg, 1.5 mmol) and cyanomethylenetri-n-butylphosphorane (494 mg, 2.1 mmol) at room temperature, and the resulting mixture was heated to 100° C. After stirring for 7 hours, the reaction solution was concentrated under reduced pressure and the resulting residue was dissolved in chloroform and washed with a 1M-aqueous sodium hydroxide solution. Extraction with chloroform was carried out again and the organic layer was dried over anhydrous magnesium sulfate. The organic layer dried was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate) to obtain trans-2-{2,2-dimethyl-5-[(4-methyl-1H-indazol-5-yl)oxy]cyclohexyl}-1H-isoindole-1,3(2H)-dione (360 mg, 61%, containing about 10% of cis isomer).

1. concentrationthe reaction solution was concentrated under reduced pressure
2. dissolutionthe resulting residue was dissolved in chloroform
3. washwashed with a 1M-aqueous sodium hydroxide solution
4. extractionExtraction with chloroform
5. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
6. customThe organic layer dried
7. concentrationwas concentrated under reduced pressure
8. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate)