Toluene → HCID 54505552, Verbindung

HRID 636830

Reaktionsgleichung

Reaktionsgleichung von HRID 636830
[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].C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.[F:45][C:46]1[CH:53]=[CH:52][C:49]([CH2:50]Br)=[CH:48][CH:47]=1>O1CCCC1.CN(C)C=O>[CH3:1][O:2][C:3]([C:5]1([CH2:50][C:49]2[CH:52]=[CH:53][C:46]([F:45])=[CH:47][CH:48]=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

7

Edukt 4

HCID 1140TolueneHCID 680214-Fluorobenzyl bromideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 44519651-Benzyl 4-tert-butyl 2-methyl piperazine-1,2,4-tricarboxylate

Produkt 1

HCID 54505552HCID 54505552, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

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 (10.5 g, 27.8 mmol), prepared as described by Bigge et al. (Tetrahedron Let. 1989, 30, 5193), in tetrahydrofuran (200 mL) under a nitrogen atmosphere was added N,N-dimethylformamide (30 mL). The reaction was cooled to about −78° C., and a 0.5 M solution of potassium bis(trimethylsilyl)amide in toluene (83 mL, 42 mmol) was added. The reaction was stirred at about −78° C. for about 1 hour, and then 4-fluorobenzyl bromide (5.2 mL, 42 mmol) was added. The reaction was stirred for about 1 hour 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 the crude product as a yellow oil. Purification by silica gel chromatography using 0-20% ethyl acetate/hexanes as eluent afforded the title compound of part 1-A (8.54 g, 63%) as a colorless oil: +APcI MS (M−Boc+H)+ 387; 1H NMR=400 MHz (CDCL3) δ: 7.45-7.30 (arom, br s, 5H), 7.00-6.80 (arom, br m, 4H), 5.35-5.05 (br m, 2H), 2.53 (br t, 1H), 1.40 (Boc, s, 9H).

Aufarbeitung

  1. stirringThe reaction was stirred for about 1 hour 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 the crude product as a yellow oil
  11. customPurification by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-5e588bb12b574a7abf3ae99bcbf219f4
Quelldatensatz
uspto-grants-2001_02
Patentnummer
US06194578B1

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