34941-91-8

124-38-9

929022-76-4

Step A: Synthesis of 2-chloro-4-iodopyridine-3-carboxylic acid (64-2) 1. In a dry reaction flask, LDA (97 mL, 1.8 M in heptane/THF/ethylbenzene, 175 mmol) was mixed with THF (304 mL) and the solution was cooled to -78°C. 2. 2-Chloro-4-fluoropyridine (20.0 g, 152 mmol) was dissolved in 2-chloro-4-iodopyridine-3-carboxylic acid (64-2). 2. 2-chloro-4-fluoropyridine (20.0 g, 152 mmol) was dissolved in THF (50 mL) and slowly added dropwise to the cooled LDA solution described above through a constant pressure dropping funnel over 20 minutes. 3. After the dropwise addition was completed, the reaction mixture was continued to be stirred at -78°C for 1 hour. 4. the reaction mixture was slowly poured into a container with dry ice and allowed to sublimate completely. 5. Water was added to the residue and the pH was adjusted to alkaline with 1N NaOH solution. 6. Extract the mixture with ether (Et2O) and discard the organic layer. 7. The aqueous layer was acidified to pH < 7 with 1N HCl solution and extracted with ethyl acetate (EtOAc). 8. The organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate (MgSO4) and concentrated under reduced pressure to give the orange solid product 64-2 (19 g, 71.2% yield). MS (ESI): m/z = 176.0 ([M+H]+).