Dimethylformamide → 2-Benzyl-piperazine-1,2,4-tricarboxylic acid 1-benzyl ester 4-tert-butyl ester 2-methyl ester

HRID 583846

Reaktionsgleichung

Reaktionsgleichung von HRID 583846
[CH3:1][O:2][C:3]([CH:5]1[CH2:10][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:8][CH2:7][N:6]1[C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])=[O:4].CN(C)C=O.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:43](Br)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>O1CCCC1>[CH3:1][O:2][C:3]([C:5]1([CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH2:10][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:15])[CH3:16])=[O:12])[CH2:8][CH2:7][N:6]1[C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])=[O:4]

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 7498Benzyl BromideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 44519651-Benzyl 4-tert-butyl 2-methyl piperazine-1,2,4-tricarboxylate

Produkt 1

HCID 536928572-Benzyl-piperazine-1,2,4-tricarboxylic acid 1-benzyl ester 4-tert-butyl ester 2-methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a stirred solution of piperazine-1,2,4-tricarboxylic acid 1-benzyl ester 4-tert-butyl ester 2-methyl ester (20.0 g, 53 mmol), prepared as described by Bigge et al. (Tetrahedron Let. 1989, 30, 5193), in tetrahydrofuran (500 mL) was added N,N-dimethylformamide (50 mL). The reaction was cooled to about −78° C., and a 1M solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (80 mL) was added. The reaction was stirred at about −78° C. for about 1 hour, and then benzyl bromide (9.4 mL, 79 mmol) was added. The reaction was stirred for about 30 minutes more at about −78° C., then warmed to room temperature and stirred overnight. The reaction was quenched with saturated sodium bicarbonate solution, and the mixture was extracted three times with ethyl acetate. The combined organic layers were extracted twice with water, brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give 31 g of crude product. Purification by silica gel chromatography using 10-20% ethyl acetate/hexanes as eluent afforded the title compound of part 1-A (20.33 g, 82%): +APcl MS (M−55)+ 413, (M−99)+ 369; 1H NMR=400 MHz (CDCl3) δ: 7.37 (arom, m, 5H), 7.22 (arom, m, 3H), 7.00 (arom, m, 2H), 1.41 (BOC, d, 9H).

Aufarbeitung

  1. stirringThe reaction was stirred for about 30 minutes more at about −78° C.
  2. temperaturewarmed to room temperature
  3. stirringstirred overnight
  4. customThe reaction was quenched with saturated sodium bicarbonate solution
  5. extractionthe mixture was extracted three times with ethyl acetate
  6. extractionThe combined organic layers were extracted twice with water, brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give 31 g of crude product
  11. customPurification by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-ee3ffe7fbfde4947a56713fff9422247
Quelldatensatz
uspto-grants-2005_08
Patentnummer
US06924280B2

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