تفاعل #69748

معادلة التفاعل

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

المردود 57.0%

المذيبات

THF

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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.

المصدر