Tert-butyl 4-cyanopiperidine-1-carboxylate → 1,1-Dimethylethyl 4-(5-chloro-3-fluoro-2-pyridinyl)-4-cyano-1-piperidinecarboxylate

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Reaction Conditions

Reaction Steps

Potassium hexamethyldisilazane (1.34 ml, 0.5 M solution in toluene) was slowly added to a solution of 5-Chloro-2,3-difluoro-pyridine (0.1 g) and N-Boc-4-Cyano-Piperidine (0.14 g) in 3 ml toluene at 0° C., under nitrogen. The mixture was stirred at 0° C. for 1 hr. After cooling, the reaction mixture was quenched in 1N HCl. The aqueous phase was extracted twice with ethyl acetate and the combined organic were washed with water, dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by chromatography [SiO2; hexane-ethyl acetate-hexane (4:1)] to give 111 mg (49%) of 5-chloro-4′-cyano-3-fluoro-3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert -butyl ester; MS (ES+) 240 (M-Boc+H+).

Provenance & Evidence