Sodium hydride → 4-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1373638Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1373638
[F:1][C:2]1([F:12])[O:6][C:5]2[CH:7]=[CH:8][CH:9]=[C:10]([NH2:11])[C:4]=2[O:3]1.[C:13]([O:17][C:18](=[O:26])[N:19]([CH2:23][CH2:24]Cl)[CH2:20][CH2:21]Cl)([CH3:16])([CH3:15])[CH3:14].[H-].[Na+]>CN(C=O)C>[C:13]([O:17][C:18]([N:19]1[CH2:23][CH2:24][N:11]([C:10]2[C:4]3[O:3][C:2]([F:1])([F:12])[O:6][C:5]=3[CH:7]=[CH:8][CH:9]=2)[CH2:21][CH2:20]1)=[O:26])([CH3:16])([CH3:15])[CH3:14]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 27368912,2-Difluoro-1,3-dioxaindan-4-amineHCID 11230235N-BOC-N,N-Bis(2-chloroethyl)amine

Produkt 1

HCID 694174874-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-piperazine-1-carboxylic acid tert-butyl esterAusbeute 22,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

An intermediate compound, 1-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-piperazine, was produced as follows: To the mixture of 2,2-difluoro-benzo[1,3]dioxol-4-ylamine (27 g, 0.156 mol) and bis-(2-chloro-ethyl)-carbamic acid tert-butyl ester (75.5 g, 0.31 mol) in DMF (500 mL) was added NaH (15.6 g, 60% oil dispersion, 0.39 mol) at 0° C. and the resulting mixture was stirred at room temperature for 24 h until LCMS indicated the starting material disappeared. The reaction was quenched with aq. NH4Cl, extracted with EtOAc, washed with brine, dried and concentrated. The residue was purified by flash chromatography (Et3N:EtOAc:heptane/1:10:100) to afford 4-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (12.0 g, 22%) as colorless crystals.

Aufarbeitung

  1. customThe reaction was quenched with aq. NH4Cl
  2. extractionextracted with EtOAc
  3. washwashed with brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (Et3N:EtOAc:heptane/1:10:100)

Quellen und Nachweise

ORD-Eintrag
ord-8e099b4593f5486a974eba2aa0e3f8f2
Quelldatensatz
uspto-grants-2007_01
Patentnummer
US07160888B2

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