Sodium Carbonate → 4-(1-tert-Butoxycarbonyl-1,2,3,6-tetrahydropyridin-4-yl)benzoic acid

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Reaction Steps

To a solution of tert-butyl 1,2,3,6-tetrahydro-4-[(trifluoromethyl)sulfonyloxy]pyridine-1-carboxylate (2.63 g, 7.9 mmol, reference example 76) in dimethdxyethane (21 mL) is added 4-carboxybenzeneboronic acid (1.44 g, 8.7 mmol), 2M aqueous sodium carbonate (17.4 mL) and lithium chloride (0.99 g, 24 mmol). The mixture is degassed and then tetrakis(triphenylphosphine)palladium (450 mg, 0.4 mmol) added, the reaction is degassed again and then heated at reflux 6 h. The reaction is filtered and the solid washed with EtOAc. The organic phase is washed with 0.5 N HCl, dried (MgSO4), concentrated and purified by column chromatography (silica, 3% MeOH/CH2Cl2/0.1%HOAc) providing a semi-purified product. This material is titurated with ether and a small amount of CH2Cl2 to provide 0.27 g of the title compound as a white solid: m.p. 200-209 (dec); 1H NMR (300 MHz, CDCl3) d 8.07 (d, J=8.4 Hz, 2H), 7.47 (d, J=8.4 Hz, 2H), 6.20 (bs, 1H), 4.15-4.00 (m, 2H), 3.66 (t, J=5.6 Hz, 2H), 2.60-2.52 (m, 2H), 1.50 (s, 9H); MS (ion spray) m/z 304 (M+H+).

Provenance & Evidence