Toluene → Ethyl 1-(5-fluoropyridin-2-yl)piperidine-4-carboxylate

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Reaction Conditions

Reaction Steps

To a stirred solution of piperidine-4-carboxylic acid ethyl ester (14.3 g, 0.091 mol) and 2-chloro-5-fluoro-pyridine (10 g, 0.076 mol) in toluene (100 mol) was added NaOtBu (8.77 g, 0.091 mol), BINAP (1.42 g, 2.28 mmol) and tris(dibenilideneacetone)dipalladium(0) (1.39 g, 1.52 mmol). The reaction mixture was heated at 75° C. for 2 hours, cooled down to RT, and diluted with AcOEt (100 mL) and H2O (100 mL). The organic layer was separated and washed with brine, dried over Na2SO4 and concentrated under vacuo. Column chromatography (SiO2, EtOAc/heptane, 1:9 to 1:1) yielded 12.5 g (65%) of 5′-fluoro-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carboxylic acid ethyl ester as a yellow oil. ES-MS m/e: 253.3 (M+H+).

Provenance & Evidence