52133-67-2

105-56-6

2032-35-1

52133-67-2

Method AI: Synthesis of ethyl 2-cyano-4,4-diethoxybutyrate (xlii-a): In a dry reaction flask, ethyl 2-cyanoacetate (11.4 g, 101 mmol, 5.0 eq.), potassium carbonate (2.8 g, 20 mmol, 1.0 eq.), and sodium iodide (200 mg, 1.3 mmol, 0.06 eq.) were added in sequence. Subsequently, 2-bromo-1,1-diethoxyethane (4 g, 20 mmol, 1.0 eq.) was slowly added to the mixture. The reaction mixture was refluxed at 145°C for 4 hours with reference to J. Chem. Soc., 1960,131-138. After completion of the reaction, it was cooled to room temperature and the product was purified by silica gel column chromatography with petroleum ether/ethyl acetate as eluent (gradient elution: 80:1→40:1→40:1) to give 3.57 g of the target compound xii-a as a colorless oil in 78% yield.1H NMR (400 MHz, CDCl3): δ 4.70 (t, J=5.6 Hz, 1H), δ 4.26 (q, J=7.2Hz, 2H), 3.78-3.64 (m, 3H), 3.62-3.45 (m, 2H), 2.35-2.14 (m, 2H), 1.34 (q, J=7.2Hz, 3H), 1.25-1.16 (m, 6H).