Potassium Carbonate → (5-Chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-phenylsulfamoyl)-acetic Acid

HRID 11634

Reaktionsgleichung

Reaktionsgleichung von HRID 11634
[NH2:1][C:2]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:3]=1[O:4][CH2:5][C:6]([N:8]1[CH2:13][C@H:12]([CH3:14])[N:11]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH2:10][C@H:9]1[CH3:23])=[O:7].C(=O)([O-])[O-].[K+].[K+].C([O:37][C:38](=[O:44])[CH2:39][S:40](Cl)(=[O:42])=[O:41])C.CN(C1C=CC=CN=1)C.O.[OH-].[Li+]>CN(C)C=O.C(OCC)(=O)C.O>[Cl:28][C:26]1[CH:25]=[CH:24][C:3]([O:4][CH2:5][C:6]([N:8]2[CH2:13][C@H:12]([CH3:14])[N:11]([CH2:15][C:16]3[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=3)[CH2:10][C@H:9]2[CH3:23])=[O:7])=[C:2]([NH:1][S:40]([CH2:39][C:38]([OH:44])=[O:37])(=[O:42])=[O:41])[CH:27]=1

Komponenten

9

Edukt 5

HCID 11430Potassium CarbonateHCID 218852-DimethylaminopyridineHCID 168937Lithium hydroxide, monohydrateHCID 12225100Ethyl (chlorosulfonyl)acetateHCID 540805932-(2-amino-4-chloro-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone

Produkt 1

HCID 69655531(5-Chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-phenylsulfamoyl)-acetic Acid

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 2-(2-amino-4-chloro-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (0.030 g, 0.074 mmol) in dimethylformamide (0.5 ml) was added potassium carbonate (0.030 g, 0.239 mmol), chlorosulfonyl-acetic acid ethyl ester (0.02 g, 0.12 mmol) (for preparation, see: Helv. Chim. Acta., (1997) 80, 671 and Bull. Soc. Chim. Fr. (1975), 807) in dimethylformamide (0.5 ml) and finally catalytic dimethylaminopyridine. After 23 hours the reaction was diluted with ethyl acetate and washed with pH 7.0 phosphate buffer (0.05 M). The organic layer was dried over magnesium sulfate, filtered and concentrated. The crude ester was then dissolved in 1:1 tetrahydrofuran:water (0.5 ml) and lithium hydroxide hydrate (0.004 g, 0.095 mmol) was added. After 19 hours the reaction was concentrated and the title compound purified by silica gel chromatography (0.006 g, LRMS: 528.3).

Aufarbeitung

  1. washwashed with pH 7.0 phosphate buffer (0.05 M)
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe crude ester was then dissolved in 1:1 tetrahydrofuran
  6. concentrationAfter 19 hours the reaction was concentrated
  7. customthe title compound purified by silica gel chromatography (0.006 g, LRMS: 528.3)

Quellen und Nachweise

ORD-Eintrag
ord-51ce9bb9875247e18ea225cd6ad21a82
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07098212B2

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