反应详情

Sodium hydride (60%, oily) (31 mg, 0.78 mmol) was suspended in dimethylformamide (3 mL), and the suspension was stirred at room temperature under a nitrogen atmosphere. To the suspension was added a solution of trans-(2-{4-[2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazin-1-ylmethyl}cyclopropyl)methanol (60 mg, 0.156 mmol) produced in Example (91a) in dimethylformamide (3 mL), and the mixture was stirred for 30 minutes under the same conditions. The reaction mixture was cooled in ice water, and then iodomethane (0.015 mL, 0.241 mmol) was added. The reaction mixture was then stirred for 3 hours and 30 minutes while increasing the temperature to room temperature. The reaction mixture was cooled at an external temperature of 0° C., and water was carefully added while blowing nitrogen. Then, ethyl acetate and water were added thereto and extraction was performed with ethyl acetate. The separated organic layer was washed twice with water and then once with brine, and dried over anhydrous sodium sulfate. The desiccant was filtered off and the filtrate was concentrated under reduced pressure. The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane) to give 28 mg of trans-1-(2-methoxymethylcyclopropylmethyl)-4-[2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazine as a colorless oil.

1. stirringthe mixture was stirred for 30 minutes under the same conditions
2. stirringThe reaction mixture was then stirred for 3 hours and 30 minutes
3. temperaturewhile increasing the temperature to room temperature
4. additionwas carefully added
5. extractionextraction
6. washThe separated organic layer was washed twice with water
7. dry with materialonce with brine, and dried over anhydrous sodium sulfate
8. filtrationThe desiccant was filtered off
9. concentrationthe filtrate was concentrated under reduced pressure
10. customThe resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane)