Synthesis
The general procedure for the synthesis of 2-chloro-N-(2-methoxyphenyl)acetamide from o-methoxyaniline (0.5 g, 4.05 mmol) and chloroacetyl chloride (0.387 mL, 4.87 mmol) was as follows: to a solution of acetonitrile (10.0 mL) of o-methoxyaniline under argon gas protection was added N,N-diisopropyl ethylamine (DIPEA, 1.56 mL 8.93 mmol), followed by slow dropwise addition of chloroacetyl chloride. After the dropwise addition, the reaction mixture was stirred at room temperature for 1 hour. The reaction process was monitored by thin layer chromatography (TLC). After completion of the reaction, the reaction mixture was concentrated and purified by column chromatography (eluent: 20% ethyl acetate/hexane) to afford the target compound 2-chloro-N-(2-methoxyphenyl)acetamide as a brown solid (0.72 g, 89.05% yield). The structure of the product was confirmed by 1H NMR (CDCl3, 400 MHz): δ 8.96 (s, 1H), 8.35 (dd, J = 1.6, 8.0 Hz, 1H), 7.14-7.10 (m, 1H), 7.02-6.97 (m, 1H), 6.94-6.91 (m, 1H), 4.21 (s, 2H), 3.93 (s, 3H).
References
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[2] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 24, p. 6885 - 6892
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