Triphenylphosphine → N-Ethylphthalimide

関与物質

反応手順

To a cooled (5° C.) suspension of 0.914 g (2.7 mmol) of 6-(chlorophenyl)-2-methanesulfonyl-pyrido[2,3-d]pyrimidin-7-ol, 1.041 g (5.4 mmol) of N-(2-hydroxyethyl)-phthalimide, 1.43 g (5.4 mmol) of triphenylphosphine in 15 mL of 1,4-dionxane was added dropwise a solution of 0.95 g (0.86 mL, 5.4 mmol) diethylazodicarboxylate in 5 mL of 1,4-dioxane over a period of 30 min. After addition was completed, the ice-water cooling bath was removed. The suspension soon turned into a clear light brown solution. This was allowed to stir at room temperature overnight. The reaction mixture was concentrated under reduced pressure and purified by column chromatography on 120 g of silica gel using 90:10:0.5 ethyl acetate/dichloromethane/ammonium hydroxide to obtain 0.38 g of the N-ethylphthalimide intermediate. A mixture of 0.18 g (0.35 mmol) of this intermediate and 0.05 g (0.42 mmol) of trans-4-aminocyclohexanol in 1 mL of NMP was heated to 120° C. for 30 min. The reaction mixture was cooled, diluted with 75 mL of water and extracted with ethyl acetate (3×75 mL). The combined ethyl acetate solution was washed with water (3×75 mL), brine, dried, filtered and concentrated. The material was purified by column chromatography on 40 g of silica eluting with 5% methanol/dichloromethane affording 45 mg of compound 65. (mass spec. MH+=544, mp 208-210° C.).

情報源と証拠