Synthesis
To a solution of ethyl 4-aminobenzoate (2.0 mmol) in acetonitrile (2 mL) was added N-chlorosuccinimide (NCS, 2.05 mmol). The reaction mixture was heated to reflux for 5 hours. Upon completion of the reaction, the reaction mixture was extracted with ethyl acetate and the organic layer was washed with 5% sodium hydroxide solution and subsequently dried with anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure to give the crude product. Purification by recrystallization in hexane afforded ethyl 4-amino-3-chlorobenzoate (27c) as purple crystals (melting point 81-83 °C) in 86% yield. The structure of the product was confirmed by 1H NMR (300 MHz, CDCl3) and 13C NMR (75 MHz, CDCl3): 1H NMR δ 1.33 (t, 3H, J=7.0 Hz, CH3), 4.29 (q, 2H, J=7.0 Hz, CH2), 6.70 (d, 1H, J=8.5 Hz, Ar-H), 7.72 (dd , 1H, J=8.4,1.9 Hz, Ar-H), 7.92 (d, 1H, J=1.9 Hz, Ar-H); 13C NMR δ 14.30, 60.62, 114.35, 118.06, 120.63, 129.52, 131.12, 146.97, 165.74.
References
[1] Organic Letters, 2008, vol. 10, # 1, p. 113 - 116
[2] Journal of the Brazilian Chemical Society, 2018, vol. 29, # 1, p. 109 - 124
[3] Journal of Medicinal Chemistry, 2004, vol. 47, # 27, p. 6973 - 6982
[4] Patent: US5502073, 1996, A
[5] Patent: US5516774, 1996, A
