تفاعل #60509

معادلة التفاعل

Sodium hydride

iodomethane

trans-(2-{4-[2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazin-1-ylmethyl}cyclopropyl)methanol

→

trans-1-(2-methoxymethylcyclopropylmethyl)-4-[2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazine

المردود 45.0%

المذيبات

water

dimethylformamide

dimethylformamide

—

ice water

water

ethyl acetate

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGthe mixture was stirred for 30 minutes under the same conditions
2. 2
   workup.STIRRINGThe reaction mixture was then stirred for 3 hours and 30 minutes
3. 3
   درجة الحرارةwhile increasing the temperature to room temperature
4. 4
   workup.ADDITIONwas carefully added
5. 5
   استخلاصextraction
6. 6
   غسيلThe separated organic layer was washed twice with water
7. 7
   تجفيفonce with brine, and dried over anhydrous sodium sulfate
8. 8
   ترشيحThe desiccant was filtered off
9. 9
   تركيزthe filtrate was concentrated under reduced pressure
10. 10
    أخرىThe resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane)

الإجراء التجريبي

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 0C, 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.

المصدر