Diisopropylethylamine → 1-(4-Bromo-2-ethylphenyl)-4-(toluene-4-sulfonyl)piperazine

HRID 1803948

Reaktionsgleichung

Reaktionsgleichung von HRID 1803948
[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([CH2:9][CH3:10])[CH:3]=1.C(N(C(C)C)CC)(C)C.Cl[CH2:21][CH2:22][N:23]([CH2:34][CH2:35]Cl)[S:24]([C:27]1[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=1)(=[O:26])=[O:25]>>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([N:6]2[CH2:35][CH2:34][N:23]([S:24]([C:27]3[CH:28]=[CH:29][C:30]([CH3:33])=[CH:31][CH:32]=3)(=[O:26])=[O:25])[CH2:22][CH2:21]2)=[C:4]([CH2:9][CH3:10])[CH:3]=1

Komponenten

4

Edukt 3

HCID 81531DiisopropylethylamineHCID 96039N,N-bis(2-chloroethyl)-p-toluenesulphonamideHCID 28012834-Bromo-2-ethylaniline

Produkt 1

HCID 673813351-(4-Bromo-2-ethylphenyl)-4-(toluene-4-sulfonyl)piperazine

Versuchsvorschrift

A mixture of 4-bromo-2-ethylaniline (1.4 mL), diisopropylethylamine (4.4 mL) and N,N-bis(2-chloroethyl)-4-methylbenzenesulfonamide (3 g) was refluxed for 5 hr. After cooling, the solvent was evaporated, and the residue was purified by column chromatography (chloroform) to give 1-(4-bromo-2-ethylphenyl)-4-(toluene-4-sulfonyl)piperazine (3 g). To a mixture of 1-(4-bromo-2-ethylphenyl)-4-(toluene-4-sulfonyl)piperazine (3 g), methylboronic acid (1.2 g), palladium acetate (112 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (411 mg) and potassium fluoride (2.3 g) was added tetrahydrofuran (30 mL), and the mixture was refluxed for 8 hr. After cooling, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (chloroform) to give 1-(2-ethyl-4-methylphenyl)-4-(toluene-4-sulfonyl)piperazine (2.9 g). A mixture of 1-(2-ethyl-4-methylphenyl)-4-(toluene-4-sulfonyl)piperazine (2.9 g), hydrobromic acid (16 mL) and acetic acid (16 mL) was refluxed for 8 hr. After cooling, the reaction mixture was alkalified with 1N aqueous sodium hydroxide solution, and the mixture was extracted with chloroform. The organic layer was washed with saturated brine, and the solvent was evaporated. 4N hydrogen chloride/ethyl acetate (3 mL) was added and the mixture was filtered to give 1-(2-ethyl-4-methylphenyl)piperazine hydrochloride (1.7 g). To a mixture of 4-bromo-2-methanesulfonylbenzoic acid (1.1 g), 1-(2-ethyl-4-methylphenyl)piperazine hydrochloride (963 mg) and 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (DMT-MM) (1.5 g) were added chloroform (6 mL), methanol (6 mL) and N-methylmorpholine (440 μL), and the mixture was stirred at room temperature overnight. After evaporation of the solvent, the residue was purified by column chromatography (chloroform) to give the title compound (1.8 g).

Aufarbeitung

  1. temperaturewas refluxed for 5 hr
  2. temperatureAfter cooling
  3. customthe solvent was evaporated
  4. customthe residue was purified by column chromatography (chloroform)

Quellen und Nachweise

ORD-Eintrag
ord-dd04c743044c4e1481bae294deece72c
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08354401B2

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