tert-Butyl acrylate → tert-Butyl (2E)-3-(5-benzyloxy-6-methylpyridin-2-yl)acrylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 828 mg (2.55 mmol) of 2-methyl-3-benzyloxy-6-iodopyridine (from Step B), 746 μL (5.09 mmol) of tert-butyl acrylate, 535 mg (6.37 mmol) of sodium bicarbonate, 708 mg (255 mmol) of tetrabutylammonium chloride, and 20 mg of crushed 4 A molecular sieve in 10 mL of DMF was added 29 mg (0.13 mmol) of palladium acetate. After stirring at 60° C. for 5 h, the reaction mixture was cooled to rt, diluted with EtOAc (20 mL), and filtered through a cake of Celite. The filtrate was washed with brine (100 mL), H2O (3×100 mL), and brine (100 mL). The organic layer was dried over Na2SO4 and concentrated. Chromatography on a Biotage 40M cartridge using 2:23 v/v EtOAc/hexanes as the eluant afforded 703 mg of the title compound: 1H NMR (500 MHz, CDCl3) δ 1.52 (s, 9H), 2.53 (s, 3H), 5.09 (s, 2H), 6.70 (d, J=15.6, 2H), 7.06 (d, J=8.5, 1H), 7.18 (d, J=8.5, 1H), 7.37-7.42 (m, 5H), 7.52 (d, J=15.8, 2H).

Provenance & Evidence