Phosphate → 1-Benzyl-4-bromomethyl-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid ethyl ester

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Reaction Steps

1-Benzyl-2-oxo-1,2-dihydro-pyridine-3,4-dicarboxylic acid 3-ethyl ester (1.8 g, 5.98 mmol) was dissolved in 50 mL of CH2Cl2. Oxalyl chloride (5.2 mL, 59.8 mmol) and DMF (2 drops) were added, and the mixture was stirred for 3 h. Solvent and excess oxalyl chloride were removed by evaporation in vacuo, and to the residue was added a solution of NaCNBH3 (750 mg, 12 mmol) in THF (40 mL). The resulting suspension was stirred at r.t. for 16 h. The reaction mixture was cooled in an ice bath, and then poured into a pre-cooled, vigorously stirring pH 4.9 phosphate buffer (300 mL). The resulting mixture was extracted several times with benzene, and the combined organic layer was washed with ice-cold water and dried over MgSO4. Evaporation of the solvent at reduced pressure gave a yellow oil, which was dissolved in 30 mL of CH2Cl2. The solution was cooled in at ice bath, and triphenylphosphine (1.64 g, 6.27 mmol) and carbon tetrabromide (2.08 g, 6.27 mmol) were added. The mixture was then stirred at r.t. for 16 h. Solvent was evaporated in vacuo, and the residue was purified by silica gel chromatography (0-60% EtOAc/hexanes) to give 860 mg of the title compound as an orange oil. 1H NMR (CDCl3, 200 MHz): δ=7.20-7.45 (m, 6H), 6.20 (d, 1H, J=7.0 Hz), 5.12 (s, 2H), 4.43 (q, 2H, J=7.0 Hz), 4.28 (s, 2H), 1.42 (t, 3H, J=7.0 Hz).

Provenance & Evidence