反应详情

1-(2,4-Dimethoxy-benzyl)-2-oxo-1,2-dihydro-pyridine-3,4-dicarboxylic acid 4-ethyl ester (13.2 g, 36.5 mmol) was dissolved in 280 mL of CH2Cl2. Oxalyl chloride (32 mL, 365 mmol) and DMF (3 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 (4.6 g, 73 mmol) in THF (250 mL). The resulting yellow 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 (900 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 viscous oil, which was dissolved in 260 mL of CH2Cl2. The solution was cooled in at ice bath, and triphenylphosphine (10.5 g, 39.9 mmol) and carbon tetrabromide (13.2 g, 39.9 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 4.43 g of the title compound as a light yellow solid. 1H NMR (CDCl3, 200 MHz): δ=7.35-7.50 (m, 2H), 6.40-6.55 (m, 3H), 5.07 (s, 2H), 4.87 (s, 2H), 4.39 (q, 2H, J=7.0 Hz), 3.81 (s, 3H), 3.80 (s, 3H), 1.41 (t, 3H, J=7.0 Hz).

1. customSolvent and excess oxalyl chloride were removed by evaporation in vacuo
2. stirringThe resulting yellow suspension was stirred at r.t. for 16 h
3. temperatureThe reaction mixture was cooled in an ice bath
4. additionpoured into a pre-cooled
5. extractionThe resulting mixture was extracted several times with benzene
6. washthe combined organic layer was washed with ice-cold water
7. dry with materialdried over MgSO4
8. customEvaporation of the solvent at reduced pressure
9. customgave a viscous oil, which
10. temperatureThe solution was cooled in at ice bath
11. stirringThe mixture was then stirred at r.t. for 16 h
12. customSolvent was evaporated in vacuo
13. customthe residue was purified by silica gel chromatography (0-60% EtOAc/hexanes)