1. tert-Butyl malonate (2.64 g, 15.14 mmol) was dissolved in tetrahydrofuran (THF, 50 mL). Sodium hydride (0.605 g, 15.14 mmol) was added in batches at 0 °C, followed by stirring the reaction mixture for 15 min at room temperature.
2. 2-chloro-5-nitropyridine (2.01 g, 12.61 mmol) was dissolved in THF (10 mL), added to the above mixture, and stirring was continued for 4 hours at room temperature.
3. Upon completion of the reaction, the reaction was quenched with saturated aqueous ammonium chloride solution followed by three extractions with ethyl acetate (EtOAc). The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated.
4. The resulting residue was dissolved in a solvent mixture of dichloromethane (DCM) and trifluoroacetic acid (TFA) (30 mL, 2:1, v/v/v) and stirred for 1.5 hours.
5. The reaction mixture was diluted with 1.5 M potassium phosphate solution and again extracted three times with EtOAc. The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated.
6. The residue was dissolved in dichloromethane and purified by silica gel column chromatography (80 g silica gel, elution gradient: 30-100% EtOAc in hexane solution).
7. The eluate containing the target product was collected and concentrated to give Intermediate I-109A (1.06 g, 5.40 mmol, 42.8% yield) as a yellow oil.
LC-MS analysis (Method H): MS (ESI) m/z: 197.0 [M + H]+.
1H NMR (400 MHz, CDCl3) δ: 9.41 (d, J = 2.6 Hz, 1H), 8.49 (dd, J = 8.6, 2.6 Hz, 1H), 7.56 (d, J = 8.6 Hz, 1H), 4.02 (s, 2H), 3.78 (s, 3H).
