Реакция #69748

Уравнение реакции

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

Выход 57.0%

Растворители

THF

Условия реакции

Обработка

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

Методика

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.

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