Synthesis
1) Synthesis of intermediate A33-2: Phosphorus oxychloride (POCl3, 18.3 mL, 200 mmol) was added to a 100 mL two-necked flask and stirred 100 times. 2-Methyl-2-butenenitrile (A33-1, 10.43 g, 70%, 90 mmol) was dissolved in N,N-dimethylformamide (DMF, 15.4 mL, 200 mmol) and slowly added dropwise to the above solution. After the dropwise addition, the reaction was stirred at 110°C for 24 hours. After the reaction was completed, it was cooled to room temperature and the reaction mixture was slowly diluted with dichloromethane (100 mL) and then poured into ice water. The aqueous phase was extracted with dichloromethane (100 mL x 3), the organic phases were combined and washed with water. The organic phase was then washed with saturated saline (200 mL x 3), dried over anhydrous sodium sulfate, filtered to remove the desiccant, and the solvent was removed by rotary evaporation. The residue was purified by column chromatography (eluent: petroleum ether/ethyl acetate=10:1) to give a white solid product (2.9 g, 21% yield).
