Reaktion #69748

Reaktionsgleichung

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

Ausbeute 57.0%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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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