Ammonia → 4-(6-Methoxy-pyridin-3-yl)-benzoic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

A 1.6 M solution of nBuLi in hexane (9.53 mL, 15.24 mmol) is added dropwise to a stirred solution of 5-Bromo-2-methoxy-pyridine (2.72 g, 14.52 mmol) in THF (50 mL) at −78° C. The resulting mixture is stirred for 15 minutes at −78° C. To this is added a 0.5 M solution of ZnCl2 in THF (29.04 mL, 14.52 mmol) and the resulting mixture allowed to warm to room temperature. In a separate flask tetrakis(triphenylphosphine)palladium(O) (0.58 g, 0.50 mmol) is stirred in THF (10 mL). To this is added 4-ethyl-iodobenzoate (3.61 g, 13.07 mmol). The contents of the two flasks are combined and stirred for 1 hour at room temperature. A 5% solution of ammonia in water (150 mL) is added with stirring. The mixture is extracted with EtOAc (3×). The organics are combined and dried over MgSO4, filtered and concentrated. The crude product is purified by flash chromatography (2.5% EtOAc/hexane to 5% EtOAc/hexane) to give the product as a white solid (2.43g, 9.44 mmol). 1H NMR (CDCl3, 300 MHz) d 8.41 (d, 1H), 8.08 (d, 2H), 7.82 (dd, 1H), 7.60 (d, 2H), 6.82 (d, 1H), 4.38 (q, 2H), 3.98 (s, 3H), 1.40 (t, 3H).

Provenance & Evidence