反应详情

温度

0 °C

A 1.6 M n-butyl lithium solution in THF (15 mL, 24 mmol) was added drop-wise to a solution of diisopropylamine (4.0 mL, 28.6 mmol) in THF (100 mL) under argon at 0° C. The reaction mixture was stirred at 0° C. for 30 minutes and then cooled to −78° C. and a solution of cyclopentanecarbonyl 4-(methyl)phenyl piperazine (2.97 g, 10.9 mmol) in THF (10 mL) was added over 10 minutes. The reaction mixture was stirred at −78° C. for 5 hours and then a suspension of paraformaldehyde (0.90 g, 30 mmol) in THF (10 mL) was added. The reaction mixture was allowed to warm to room temperature over 1 hour and then stirred at room temperature for 16 hours. The reaction mixture was quenched with sat. aq NH4Cl solution (10 mL), and then poured onto 1M aq Na2CO3 solution (500 mL) and extracted with EtOAc (2×500 mL). The organic layers were combined, dried (MgSO4) and concentrated in vacuo to give a yellow oil which was recrystallised from heptane/EtOAc to give (1-hydroxymethyl-cyclopentyl)-(4-(4-methylphenyl)piperazin-1-yl)-methanone (2.11 g, 64%) as a pale yellow solid.

1. temperaturecooled to −78° C.
2. stirringThe reaction mixture was stirred at −78° C. for 5 hours
3. additionwas added
4. temperatureto warm to room temperature over 1 hour
5. stirringstirred at room temperature for 16 hours
6. customThe reaction mixture was quenched with sat. aq NH4Cl solution (10 mL)
7. additionpoured onto 1M aq Na2CO3 solution (500 mL)
8. extractionextracted with EtOAc (2×500 mL)
9. dry with materialdried (MgSO4)
10. concentrationconcentrated in vacuo
11. customto give a yellow oil which
12. customwas recrystallised from heptane/EtOAc