Potassium Carbonate → 2-(4-(5-(Methoxymethyl)pyridine-3-yl)phenyl)-2-methylpropanoic acid

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Reaction Steps

3-bromo-5-(methoxymethyl)pyridine (example 32b) (4.8 g, 23.56 mmol), 2-(4-boronophenyl)-2-methylpropanoic acid (example 21b) (5.4 g, 25.92 mmol) and K2CO3 (6.5 g, 47.12 mmol) were mixed in DME (60 mL) and 15 ml of water (15 mL). The mixture was degassed for 30 minutes and Pd(PPh3)4 (0.55 g, 0.47 mmol) was added. The reaction mixture was heated to reflux for 16 hr then cooled to room temperature, and evaporated under reduced pressure. The residue was diluted with aqueous NaOH (0.5 N, 60 mL) and stirred for 30 min., and the solution extracted with ether (20 mL×3). The aqueous phase was cooled to 0° C., acidified with 2 N HCl to PH=5˜6, then extracted with EtOAc. The organic phase was washed successively with water and brine, dried over MgSO4, filtered and evaporated. The residue was triturated with hexane, filtered and evaporated to give 5.9 g of 2-(4-(5-(methoxymethyl)pyridine-3-yl)phenyl)-2-methylpropanoic acid as a light brown solid in 88% yield. 1H NMR (400 MHz, CDCl3): δ 1.66 (s, 6H), 3.44 (s, 3H), 4.54 (s, 2H), 7.54-7.56 (d, 4H), 7.92 (s, 1H), 8.56 (s, 1H), 8.76 (s, 1H). MS (M+H, 286).

Provenance & Evidence