Ammonium Chloride → tert-Butyl [5-methoxy-2-(2-oxo-2-thiophen-3-ylethyl)phenyl]carbamate

Participants

Reaction Steps

Under an argon atmosphere, to a solution of tert-butyl (5-methoxy-2-methylphenyl)carbamate (2.00 g) in tetrahydrofuran (38 mL) was added dropwise sec-butyllithium (1.00 mol/L hexane-cyclohexane solution, 18.5 mL) at −45° C., and this mixture was stirred for 30 minutes. Then, a solution of N-methoxy-N-methylthiophene-3-carboxamide (1.59 g) in tetrahydrofuran (4.1 mL) was added dropwise thereto, and this mixture was stirred at −45° C. for 30 minutes and at room temperature for additional 1 hour. 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 saturated brine, 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 (1.87 g). 1H-NMR (CDCl3) δ ppm: 1.53 (9H, s), 3.79 (3H, s), 4.08 (2H, s), 6.59 (1H, dd, J=2.8, 8.5 Hz), 7.08 (1H, d, J=8.5 Hz), 7.35 (1H, dd, J=2.8, 5.1 Hz), 7.43-7.56 (1H, br), 7.60 (1H, dd, J=1.3, 5.1 Hz), 7.80-8.10 (1H, br), 8.23 (1H, dd, J=1.3, 2.8 Hz).

Provenance & Evidence