4-Aminobenzonitrile → 2-(4-Cyanophenylamino)-2-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]thioacetamide

Participants

Reaction Conditions

Reaction Steps

Under nitrogen atmosphere, to a solution of the crude product containing 2-fluoro-3-(2-hydroxyethoxy)-5-methoxybenzaldehyde (16.68 g, 77.9 mmol), 4-aminobenzonitrile (9.20 g, 77.9 mmol), and guanidine hydrochloride (372 mg, 3.9 mmol) in methanol (132 mL), trimethylsilylcyanide (12.09 g, 116.9 mmol) was added at room temperature, and the resulting mixture was stirred at 40° C. for 19 hours. After cooling the mixture, tetrahydrofuran (132 mL) was added thereto under water cooling, and 20% aqueous ammonium sulfide solution (133 mL) was added dropwise to the resulting mixture, after which the resulting mixture was stirred at room temperature. After completion of the reaction, ethyl acetate and 5% saline were added to the reaction mixture, and the resulting mixture was extracted. The organic layer was washed with 5% saline and then concentrated under reduced pressure. Methanol (100 mL) was added to the residue obtained, and the resulting mixture was concentrated under reduced pressure. Further, methanol (100 mL) was added to the residue obtained, and the resulting mixture was concentrated under reduced pressure. Methanol (120 mL) was added to the residue obtained, and the resulting mixture was stirred overnight at room temperature. The precipitated solid was filtered and dried to obtain the captioned compound (20.46 g) as a pale purple solid.

Provenance & Evidence