1-Benzylpiperidine-4-carbaldehyde → (1-benzylpiperidin-4-yl)(5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)methanol

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Reaction Steps

n-BuLi (1.6 M in hexanes, 5.17 mL, 8.28 mmol) was added dropwise to a solution of 5-chloro-4-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (3.0 g, 6.9 mmol, Adesis) in THF (120 mL) at about −78° C., keeping the internal temperature of the reaction below about −70° C. during the addition. After stirring for about 40 min, 1-benzylpiperidine-4-carbaldehyde (2.1 g, 10.3 mmol) was added dropwise and the resulting mixture was stirred at about −75° C. for about 1 h. The reaction was quenched by the dropwise addition of saturated aqueous ammonium chloride (60 mL). The mixture was concentrated under reduced pressure and the remaining aqueous portion was extracted with EtOAc (125 mL). The organic layer was washed with brine (80 mL), dried over anhydrous MgSO4 and concentrated under reduced pressure to afford crude (1-benzylpiperidin-4-yl)(5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)methanol (3.53 g, quantitative) as a yellow oil: LC/MS (Table 2, Method n) Rt=1.82 min; MS m/z: 512 and 514 (M+H)+. The crude material was used directly in the next step without further purification.

Provenance & Evidence