Lithium Hexamethyldisilazide → 4-[2-(5-Bromo-2-chloropyridin-4-yl)acetyl]piperidine-1-carboxylic acid tert-butyl ester

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Reaction Steps

Lithium bis(trimethylsilyl)amide solution (1.0 M in tetrahydrofuran; 11.00 mL) is added dropwise to 5-bromo-2-chloro-4-picoline (950 mg) in tetrahydrofuran (15 mL) at −40° C. under argon atmosphere. The mixture is stirred for 2 h at −35° C. to −45° C. prior to the addition of piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (1.33 g) dissolved in tetrahydrofuran (15 mL). The reaction mixture is allowed to warm to room temperature over a period of 1 h. Ice-cold water is added and the mixture is extracted with ethyl acetate. The combined extracts are washed with brine, dried over MgSO4, and concentrated in vacuo. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 75:25→60:40) to give the title compound. LC (method 3): tR=1.43 min; Mass spectrum (ESI+): m/z=417, 419 [M+H]+.

Provenance & Evidence