反应详情

Diethyl acetamidomalonate (2.80 g, 12.9 mmole) in 10 ml dimethylformamide (dried over 4A sieves, degassed) was added dropwise over 15 minutes to a suspension of sodium hydride (515 mg of 60% NaH/oil washed free of oil with hexane, 12.9 mmole) in 10 ml DMF with external cooling to maintain reaction temperature <10° C. The reaction mixture was warmed slowly to room temperature over 45 minutes. A solution of 5-phthalimidopentyl bromide (4.24 g, 14.3 mmole) in 10 ml DMF was added in four portions at room temperature while maintaining the internal temperature <40° C. The mixture was stirred for 24 hours until complete by TLC (product Rf =0.43, starting material Rf =0.32 (B)). Upon completion, the reaction mixture pH was adjusted to "pH 6" (pH 0-14, ColorpHast indicator strips, E. Merck, moistened) with 4N HCl/dioxane. The solvent was removed by rotary evaporation to give 9.10 g of an oil, which was purified by Still column chromatography (230-400 mesh Whatman G-60 silica gel, 320 g, CHCl3 eluant). The purified adduct 5 was crystallized from ethyl acetate/cyclohexane, 1:3. Yield: 4.35 g (78%). Mp 70°-72° C. TLC: Rf =0.43 (B). MW calc 432.19, found 432. Anal. calc for C22H28N2O7 : C, 61.10; H, 6.53; `N, 6.48. Found: C, 60.72; H, 6.61: n, 6.12. HPLC 97.4%. 1H NMR (CDCl3) 1.15 (2H, m), 1.25 (6H, t, 7 Hz), 1.33 (2H, br m), 1.56 (3H, s), 1.66 (4H, m), 2.05 (1H, s), 2.32 (2H, m), 3.65 (2H, t, 7 Hz), 4.25 (4H, q, 7 Hz), 7.72 (2H, m) and 7.90 (2H, m) for AA'BB"system.

1. temperaturewith external cooling
2. temperatureto maintain
3. customreaction temperature <10° C
4. temperaturewhile maintaining the internal temperature <40° C
5. customThe solvent was removed by rotary evaporation