Sodium Bicarbonate → 3,6-dihydro-2H-[4,4]bipyridinyl-1,3'-dicarboxylic acid 1-t-butyl ester 3'-methyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of PdCl2(PPh3)2 (1.3 g, 1.9 mmol, 0.05 eq.) in THF (250 mL) was stirred for 10 minutes under nitrogen. 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid t-butyl ester (11.7 g, 37.8 mmol, 1.0 eq.) was added and the resulting solution was stirred for another 10 minutes. 4-Bromonicotinic acid methyl ester (8.2 g, 38.0 mmol, 1.0 eq.) in THF (100 mL) and NaHCO3 (16.1 g, 151.9 mmol, 4.0 eq.) in H2O (76 mL) were added, and the resulting solution was stirred for 6 hours while the temperature was maintained at 72° C. in an oil bath. The mixture was cooled to room temperature and the reaction was then quenched with water (50 mL). The resulting solution was extracted with EtOAc (150 mL). The organic layer was washed with saturated aqueous NaCl (3×200 mL), dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with EtOAc/PE (1:5) to yield 3,6-dihydro-2H-[4,4]bipyridinyl-1,3′-dicarboxylic acid 1-t-butyl ester 3′-methyl ester (8.7 g) as a white solid. ES m/z: [M+H]+319.

Provenance & Evidence