反応 #453958

反応方程式

3-[(3-chlorophenyl)thiomethyl]-N-methoxy-N-methyl-2-pyridinecarboxamide

4-chloro-1-methyl-piperidine

N2

EtOAc

→

[3-[(3-chlorophenyl)thiomethyl]-2-pyridinyl][1-methyl-4-piperidinyl]methanone

収率 64.0%

溶媒

THF

THF

反応条件

後処理

1. 1
   温度flamed out under vacuum
2. 2
   workup.ADDITIONwas added
3. 3
   workup.WAITAfter 40 minutes
4. 4
   workup.STIRRINGstirred for 5 minutes
5. 5
   抽出The organic product was extracted with EtOAc (6×100 ml)
6. 6
   洗浄the extracts were washed with brine
7. 7
   乾燥dried (Na2SO4)
8. 8
   ろ過filtered
9. 9
   濃縮concentrated
10. 10
    その他The product was chromatographed on silica
11. 11
    洗浄eluted with 5-10%MeOH/CH2Cl2

実験手順

Anhydrous CeCl3 (1.1 g, 4.46 mmol) was placed in a 50 ml 2-necked flask and flamed out under vacuum. The vacuum was replaced with N2, and dry THF (20 ml) was added. The CeCl3/THF solution was stirred at room temperature for 16 hours and then cooled to -40° C., and the Mg-Grignard reagent from 4-chloro-1-methyl-piperidine (3 ml of an 0.8M stock solution in THF) was added. The resulting solution was stirred at -40° C. for 75 minutes, and then 3-[(3-chlorophenyl)thiomethyl]-N-methoxy-N-methyl-2-pyridinecarboxamide (345 mg, 1.07 mmol) was added dropwise. After 40 minutes, the mixture was poured into 5% HCI/EtOAc, stirred for 5 minutes, and then basified to pH ~8. The organic product was extracted with EtOAc (6×100 ml), the extracts were washed with brine, dried (Na2SO4), filtered and concentrated. The product was chromatographed on silica and eluted with 5-10%MeOH/CH2Cl2 to afford [3-[(3-chlorophenyl)thiomethyl]-2-pyridinyl][1-methyl-4-piperidinyl]methanone (251 mg, 64%); HRMS, FAB, calcd. 361.1141; found. 361.1141.

出典