반응 #69748

반응 방정식

1-methyl-4-piperidone

5-bromo-2-trityl-2,3-dihydro-1H-isoindole

n-Butyllithium

→

1-methyl-4-(2-trityl-2,3-dihydro-1H-isoindol-5-yl)-piperidin-4-ol

수율 57.0%

용매

THF

반응 조건

후처리

1. 1
   workup.ADDITIONwas added over 5 minutes
2. 2
   workup.WAITAfter a further hour
3. 3
   기타the cooling bath was removed
4. 4
   기타the reaction quenched with sodium bicarbonate solution
5. 5
   추출The mixture was extracted with ethyl acetate
6. 6
   세척the organic phase was washed with brine
7. 7
   건조dried (MgSO4)
8. 8
   농축concentrated
9. 9
   기타The residue was purified by flash chromatography on silica (gradient elution with 2M methanolic ammonia/dichloromethane, 0% to 5%)

실험 절차

Under nitrogen, a solution of 5-bromo-2-trityl-2,3-dihydro-1H-isoindole (2.03 g, 4.6 mmol) in THF (20 mL) was cooled to −78° C. n-Butyllithium solution (2.5M in hexanes, 2.0 mL, 5 mmol) was added over 5 minutes, then after 10 minutes, 1-methyl-4-piperidone was added dropwise. After a further hour, the cooling bath was removed and the reaction quenched with sodium bicarbonate solution. The mixture was extracted with ethyl acetate then the organic phase was washed with brine, dried (MgSO4) and concentrated. The residue was purified by flash chromatography on silica (gradient elution with 2M methanolic ammonia/dichloromethane, 0% to 5%) to afford 1-methyl-4-(2-trityl-2,3-dihydro-1H-isoindol-5-yl)-piperidin-4-ol as a pink foam (1.25 g, 57%). 1H NMR (MeOH-d4) 7.56 (6H, dd), 7.28 (6H, t), 7.25-7.21 (2H, m), 7.15 (3H, t), 7.03 (1H, d), 3.92 (2H, s), 3.91 (2H, s), 2.70 (2H, d), 2.53 (2H, td), 2.33 (3H, s), 2.06 (2H, td), 1.70 (2H, d). MS: [M+H]+ 475.

출처