5-Bromo-2-methoxypyridine → HCID 54494848, compound

Participants

Reaction Conditions

Reaction Steps

To a cooled solution (−78° C.) of 2-methoxy-5-bromopyridine (1.13 g, 6 mmol, reference example 41a) in THF (12 mL) is added over 10 min (2.5M)n-butyllithium (2.4 mL, 6 mmol) and the resulting solution stirred for 15 min. To this solution is added dropwise (0.5M)zinc chloride (12 mL, 6 mmol) and the temperature of this arylzinc bromide allowed to warm to 0° C. with stirring. To a cooled solution (0° C.), in a separate flask, of palladium bis(dibenzylideneacetone) (288 mg, 0.5 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (276 mg, 0.5 mmol) in THF (2 mL) is added a solution of 3-chloro-4-trifluoromethanesulfonyloxy-benzoic acid methyl ester (1.59 g, 5 mmol) (reference example 39) in THF (2 mL) followed by the arylzinc bromide solution. The resulting solution is heated to 65° C. and stirred for 2.5 hours then cooled to 20° C., diluted with ether, washed with sat NH4Cl soln and brine, dried over MgSO4 and concentrated. The residue is purified by flash chromatography (eluting with 25% ether in hexanes) to give 428 mg of title compound as a yellow crystalline solid. 1H NMR(CDCl3) δ 3.95 (s, 3H), 4.00 (s, 3H), 6.84 (d, J=9 Hz, 1H), 7.40 (d, J=8 Hz, 1H), 7.72 (dd, J=9, 2 Hz, 1H), 7.98 (dd, J=8, 2 Hz, 1H), 8.15 (s, 1H), 8.25 (d, J=2 Hz, 1H). MS (EI) m/z 277 (M+).

Provenance & Evidence