1-(Methylsulfonyl)piperazine → 3-[4-(4-Methanesulfonylpiperazin-1-yl)phenyl]-3,8-diazabicyclo[3.2.1]-octane-8-carboxylic acid tert-butyl ester

HRID 40704

Reaktionsgleichung

Reaktionsgleichung von HRID 40704
[C:1]([O:5][C:6]([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][N:11]([C:16]1[CH:21]=[CH:20][C:19](Br)=[CH:18][CH:17]=1)[CH2:12]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:23][S:24]([N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)(=[O:26])=[O:25].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([O:5][C:6]([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][N:11]([C:16]1[CH:21]=[CH:20][C:19]([N:30]3[CH2:31][CH2:32][N:27]([S:24]([CH3:23])(=[O:26])=[O:25])[CH2:28][CH2:29]3)=[CH:18][CH:17]=1)[CH2:12]2)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 7091611-(Methylsulfonyl)piperazineHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 23676156Sodium t-butoxideHCID 67413521HCID 67413521, Verbindung

Produkt 1

HCID 674134673-[4-(4-Methanesulfonylpiperazin-1-yl)phenyl]-3,8-diazabicyclo[3.2.1]-octane-8-carboxylic acid tert-butyl esterAusbeute 97,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Versuchsvorschrift

3-(4-Bromophenyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (0.64 g, 1.7 mmol), 1-methanesulfonylpiperazine (0.43 g, 2.6 mmol), tris-(dibenzylideneacetone)dipalladium (0.069 g, 0.07 mmol), S-Phos (0.11 g, 0.28 mmol), and sodium t-butoxide (0.25 g, 2.6 mmol) are placed in 10 ml of toluene under nitrogen. The reaction medium is stirred at reflux for 1 h 30. After hydrolysis with a saturated aqueous NaHCO3 solution, and extraction with ethyl acetate, the organic phase is washed with a saturated aqueous sodium chloride solution and dried over MgSO4. The crude product obtained is chromatographed on silica gel, elution being carried out with a gradient of methanol/ethyl acetate in dichloromethane ranging from 100/0/0 to 7/2.5/0.5 (dichloromethane/ethyl acetate/methanol). 0.75 g of expected 3-[4-(4-methanesulfonylpiperazin-1-yl)phenyl]-3,8-diazabicyclo[3.2.1]-octane-8-carboxylic acid tert-butyl ester is obtained.

Aufarbeitung

  1. temperatureat reflux for 1 h 30
  2. customAfter hydrolysis
  3. extractionwith a saturated aqueous NaHCO3 solution, and extraction with ethyl acetate
  4. washthe organic phase is washed with a saturated aqueous sodium chloride solution
  5. dry with materialdried over MgSO4
  6. customThe crude product obtained
  7. customis chromatographed on silica gel, elution

Quellen und Nachweise

ORD-Eintrag
ord-1a01cbea3570408d92ecb309f9d6eb9a
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08530477B2

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