The general procedure for the synthesis of ethyl 4,6-dichloronicotinate from ethyl 4,6-dihydroxynicotinate was as follows: ethyl 4,6-dihydroxynicotinate (60 g, 0.328 mol) was slowly added to phosphorus triclosan (POCl3, 500 mL), followed by heating and refluxing for 2 hours. Upon completion of the reaction, the excess phosphorous trichloride was removed by distillation under reduced pressure. The residue was carefully poured into ice water, stirred for 30 min, and then extracted with ethyl acetate (EtOAc, 3 times). The organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate (MgSO4) and finally concentrated under vacuum to give ethyl 4,6-dichloronicotinate (65 g, 90% yield). The product was identified by 1H NMR (300 MHz, DMSO-d6): δ 8.80 (s, 1H), 7.95 (s, 1H), 4.34 (q, J=6.9 Hz, 2H), 1.31 (t, J=6.9 Hz, 3H); Mass Spectra (ESI) m/z: 220.1 [M+H]+.
