Step 2: Preparation of ethyl 4,6-dichloro-5-nitronicotinate (15)
To a solution of concentrated sulfuric acid (330 ml) of ethyl 4,6-dihydroxynicotinate (14) (40.0 g, 0.22 mol) cooled to 0°C, fuming nitric acid (12.7 ml) was added dropwise slowly. After the dropwise addition was completed, the reaction mixture was stirred at 0°C for 1 hour, then brought to room temperature and continued stirring for 1 hour. After completion of the reaction, the mixture was slowly poured into ice water and stirred vigorously for 10 minutes. The precipitate precipitated was collected by filtration, washed well with water and dried under vacuum to give a light yellow solid product 15 (38.7 g, 77.6% yield). The melting point of the product was 238-240 °C.
1H NMR (300 MHz, DMSO-d6) δ (ppm): 8.22 (s, 1H), 4.31 (q, J = 7.0 Hz, 2H), 1.29 (t, J = 7.0 Hz, 3H).
MS (ESI (+) 70V) m/z: 227 [M-H]-.