Sodium hydride → Methyl 6-[2-(2-tert-butoxycarbonylamino-4-methoxyphenyl)-3-oxo-3-thiophen-3-ylpropyl]pyridine-2-carboxylate

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Reaction Steps

Under an argon atmosphere, to a solution of tert-butyl [5-methoxy-2-(2-oxo-2-thiophen-3-ylethyl)phenyl]carbamate (1.87 g) in N,N-dimethylformamide (27 mL) was added sodium hydride (min. 55% in oil, 247 mg) in five divided portions under ice-cooling with stirring. This mixture was stirred for 70 minutes under ice-cooling. Then, methyl 6-chloromethylpyridine-2-carboxylate (999 mg) was added thereto in one portion, followed by stirring at 35° C. for 16 hours. To the reaction mixture were added a saturated aqueous ammonium chloride solution and water, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine successively, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (2.10 g). 1H-NMR (CDCl3) δ ppm: 1.60 (9H, s), 3.54 (1H, dd, J=10.2, 15.8 Hz), 3.61-3.75 (4H, m), 4.05 (3H, s), 5.40 (1H, dd, J=4.9, 10.2 Hz), 6.55 (1H, dd, J=2.8, 8.5 Hz), 7.00-7.12 (2H, m), 7.15-7.25 (2H, m), 7.50 (1H, dd, J=1.3, 5.0 Hz), 7.63 (1H, t, J=7.8 Hz), 7.89-7.95 (1H, m), 8.00-8.11 (2H, m).

Provenance & Evidence