Step a: Synthesis of diethyl 2-(2-bromo-4-nitrophenyl)-2-methylmalonate
1. Diethyl 2-methylmalonate (4.31 mL, 25.0 mmol) was dissolved in 25 mL of anhydrous N,N-dimethylformamide (DMF).
2. Cool the above solution to 0 °C under nitrogen protection.
3. sodium hydride (1.04 g, 26 mmol, 60% dispersed in mineral oil) was added slowly.
4. the resulting mixture was stirred at 0 °C for 3 minutes, followed by continued stirring at room temperature for 10 minutes.
5. 3-bromo-4-fluoronitrobenzene (5.00 g, 22.7 mmol) was added rapidly, at which time the color of the mixture changed to bright red.
6. After stirring for 10 minutes at room temperature, the reaction mixture was concentrated to dryness under reduced pressure.
7. The residue was partitioned between dichloromethane and saturated aqueous sodium chloride.
8. The organic layer was separated and washed twice with saturated aqueous sodium chloride.
9. The organic phases were combined and concentrated under reduced pressure to give diethyl 2-(2-bromo-4-nitrophenyl)-2-methylmalonate (8.4 g, 99% yield) as a light yellow oil, which can be used directly in the next step of the reaction.
10. It was analyzed by high performance liquid chromatography (HPLC) with a retention time of 1.86 min.
