Sodium Carbonate → 5-Nitro-3',6'-dihydro-2'H-[2,4]bipyridinyl-1'-carboxylic acid tert-butyl ester

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Reaction Steps

To a mixture of N-Boc-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (1.52 g, 4.93 mmol), 2-bromo-5-nitropyridine (1.00 g, 4.93 mmol) and PdCl2(PPh3)2 (173 mg, 0.246 mmol) under nitrogen was added 1,4-dioxane (30 mL) followed by 3 M aqueous sodium carbonate (4.93 mL, 14.8 mmol). The resulting mixture was degassed with nitrogen for 10 minutes then heated at reflux for 16 hours. On cooling EtOAc (150 mL) was added and the resulting solution was washed with water (3×50 mL), brine (50 mL) then dried (Na2SO4). The volatiles were evaporated under reduced pressure to give a brown solid that was purified using silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-30% EtOAc in petroleum benzine 40-60° C.) to give the title compound I8 as a yellow solid (1.43 g, 95%); 1H NMR (400 MHz, CDCl3) δ 9.37 (dd, J=2.6, 0.5 Hz, 1H), 8.43 (dd, J=8.8, 2.7 Hz, 1H), 7.53 (d, J=8.8 Hz, 1H), 6.95-6.83 (m, 1H), 4.20 (d, J=3.0 Hz, 2H), 3.67 (t, J=5.6 Hz, 2H), 2.70-2.63 (m, 2H), 1.49 (s, 9H). LCMS-A: rt 6.140 min; m/z 304 [M−H]−.

Provenance & Evidence