Acetamidomalonic acid diethyl ester → HCID 12531046, Verbindung

HRID 247202

Reaktionsgleichung

Reaktionsgleichung von HRID 247202
[C:1]([NH:4][CH:5]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:3])[CH3:2].[H-].[Na+].[C:18]1(=[O:34])[N:22]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]Br)[C:21](=[O:29])[C:20]2=[CH:30][CH:31]=[CH:32][CH:33]=[C:19]12.Cl.O1CCOCC1>C1(C)C=CC=CC=1.CN(C=O)C>[C:1]([NH:4][C:5]([CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][N:22]1[C:21](=[O:29])[C:20]2=[CH:30][CH:31]=[CH:32][CH:33]=[C:19]2[C:18]1=[O:34])([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 14041Acetamidomalonic acid diethyl esterHCID 24758Sodium hydrideHCID 136770N-(5-Bromopentyl)phthalimideHCID 204431481,4-Dioxane hydrochloride

Produkt 1

HCID 12531046HCID 12531046, VerbindungAusbeute 163,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-e8ee284b88294c44b9bc693390abd16d
Quelldatensatz
uspto-grants-1987_11
Patentnummer
US04705892

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