反应详情

Under a nitrogen atmosphere, a solution of 90%-cyanomethylenetri-n-butylphosphorane (1.05 g, 4.05 mmol) in toluene (5 ml) was added dropwise to a solution of cis-5-hydroxy-2,2-dimethylcyclohexanecarbonitrile (500 mg, 3.37 mmol) in toluene (12 ml) at room temperature, followed by adding thereto the 4-methyl-1H-indazol-5-ol (507 mg, 3.54 mmol) obtained in Example 402, and the resulting mixture was heated to 100° C. After 4 hours, the reaction solution was concentrated under reduced pressure, and the resulting residue was diluted with chloroform and washed with a 1M-aqueous sodium hydroxide solution. The aqueous layer was re-extracted with chloroform and then 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-dimethyl-5-[(4-methyl-1H-indazol-5-yl)oxy]cyclohexanecarbonitrile (351.1 mg, 46%).

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