2-Bromopyridine → tert-Butyl 5',6'-dihydro-[2,4'-bipyridine]-1'(2'H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (0.500 g, 1.04 mmol), 2-bromopyridine (0.164 g, 1.04 mmol), sodium carbonate (0.439 g, 4.14 mmol), tetrakis(triphenylphosphine)palladium(0) (0.120 g, 0.103 mmol) in ethylene glycol dimethyl ether (20 mL) and water (10 mL) was heated at about 85° C. for about 12 hours. The reaction mixture was allowed to cool to ambient temperature and the solvent was removed under reduced pressure. The residue was partitioned between water (25 mL) and dichloromethane (50 mL). The organic layer was separated and the aqueous layer was further extracted with dichloromethane (2×50 mL). The combined organic extracts were dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by using preparative RP-HPLC (Rainin C18, 8 mm, 300 Å, 35 cm; 5-100% acetonitrile—0.1M ammonium acetate over 20 min, 100% acetonitrile hold 10 minutes, 21 mL/min) to give tert-butyl 4-(pyridin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (0.202 g, 0.776 mmol) as a white solid; RP-HPLC (Table 1, Method b) Rt 2.78 min; m/z: (M+H)+ 261.

Provenance & Evidence