Reaktion #2027724

Reaktionsgleichung

Hydrochloric acid

1-acetyl-4-piperidone

5-Bromo-1-triisopropylsilyl-1H-indole

t-butyllithium

→

1-[4-hydroxy-4-(1-triisopropylsilyl-1H-indol-5-yl)piperidin-1-yl]ethanone

Ausbeute 21.0%

Lösungsmittel

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe yellow solution formed
2. 2
   Extraktionthe mixture extracted with ethyl acetate (2×500 ml)
3. 3
   Trocknendried (MgSO4)
4. 4
   Einengenconcentrated
5. 5
   SonstigeThe crude product was purified by flash chromatography

Vorschrift

5-Bromo-1-triisopropylsilyl-1H-indole (13.7 g, 38.9 mmol) in tetrahydrofuran (250 ml) at -78° C. was treated with t-butyllithium (45.8 ml, 77.8 mmol, 1.7M solution in pentanes) and stirred at this temperature for 15 minutes. The yellow solution formed was added to 1-acetyl-4-piperidone (5.49 g, 38.9 mmol) in tetrahydrofuran (250 ml) at -78° C., and the mixture allowed to warm to room temperature. Hydrochloric acid (40 ml, 1M) was added and the mixture extracted with ethyl acetate (2×500 ml). The extracts were combined, dried (MgSO4) and concentrated. The crude product was purified by flash chromatography using ethyl acetate as eluant, to give 1-[4-hydroxy-4-(1-triisopropylsilyl-1H-indol-5-yl)piperidin-1-yl]ethanone (3.39 g, 21%) as a white solid; δH (DMSO-d6) 1.10 (18H, d, J 7.9 Hz, 6×CH3), 1.70 (3H, m, 3×CH), 2.00 (2H, m, piperidinyl H), 2.05 (3H, s, COCH3), 2.45 (1H, m, piperidinyl H), 3.00 (1H, m, piperidinyl H), 3.30 (1H, m, piperidinyl H), 3.50 (1H, m, piperidinyl H), 3.70 (1H, m, piperidinyl H), 4.30 (1H, m, piperidinyl H), 5.00 (1H, s, OH), 6.60 (1H, d, J 2.8 Hz, ArH), 7.30 (1H, d, J 7.8 Hz, ArH), 7.35 (1H, d, J 2.2 Hz, ArH), 7.50 (1H, d, J 7.9 Hz, ArH), and 7.70 (1H, s, ArH).

Quelle