Sodium Carbonate → [5-(4-Fluorophenyl)pyridin-3-yl]methanol

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-bromo-5-hydroxymethyl-pyridine (3.3 g, 17.5 mmol) in toluene (35 ml) was added Pd(PPh3)4 (0.6 g, 0.52 mmol), an aqueous solution of Na2CO3 (17.5 ml of a 2M solution) and p-fluorphenylboronic acid (2.65 g, 19 mmol, dissolved in 8.5 ml EtOH). The mixture was heated at 80-90° C. for 1 hr and vigorously stirred. After the reaction was completed, the biphasic reaction mixture was cooled, the organic layer was collected and washed with saturated NaCl. The aqueous layer was washed with EtOAc and the combined organic layers were dried on Na2SO4. The drying agent was removed by filtration and the solvent was evaporated in vacuo to give a dark oil which was purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH/NH4OH, 95/4.5/0.5) and yielded 3-(p-fluorophenyl)-5-hydroxymethyl-pyridine (3.0 g, 84%). The product was converted into its monohydrochloride salt; the residue was dissolved in Et2O and treated with 16.5 eq of ethanolic HCl. The product 3-(p-fluorophenyl)-5-hydroxymethyl-pyridinium hydrochloride Q4-OH.HCl precipitated as a white solid which was collected by filtration and subsequent drying.

Provenance & Evidence