Reacción #69748

Ecuación de reacción

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

Rendimiento 57.0%

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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.

Fuente