Thioglycolic Acid → ethyl 3-{2-fluoro-4-[({4'-[(4-hydroxy-1-oxidotetrahydro-2H-thiopyran-4-yl)methoxy]-2',6'-dimethylbiphenyl-3-yl}methyl)amino]phenyl}propanoate

HRID 508106

Reaktionsgleichung

Reaktionsgleichung von HRID 508106
[F:1][C:2]1[CH:7]=[C:6]([N:8]([CH2:21][C:22]2[CH:23]=[C:24]([C:28]3[C:33]([CH3:34])=[CH:32][C:31]([O:35][CH2:36][C:37]4([OH:44])[CH2:42][CH2:41][S:40](=[O:43])[CH2:39][CH2:38]4)=[CH:30][C:29]=3[CH3:45])[CH:25]=[CH:26][CH:27]=2)S(C2C=CC=CC=2[N+]([O-])=O)(=O)=O)[CH:5]=[CH:4][C:3]=1[CH2:46][CH2:47][C:48]([O:50][CH2:51][CH3:52])=[O:49].SCC(O)=O.O.[OH-].[Li+]>CN(C)C=O.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([NH:8][CH2:21][C:22]2[CH:23]=[C:24]([C:28]3[C:29]([CH3:45])=[CH:30][C:31]([O:35][CH2:36][C:37]4([OH:44])[CH2:42][CH2:41][S:40](=[O:43])[CH2:39][CH2:38]4)=[CH:32][C:33]=3[CH3:34])[CH:25]=[CH:26][CH:27]=2)[CH:5]=[CH:4][C:3]=1[CH2:46][CH2:47][C:48]([O:50][CH2:51][CH3:52])=[O:49]

Komponenten

6

Edukt 3

HCID 1133Thioglycolic AcidHCID 168937Lithium hydroxide, monohydrateHCID 68718060ethyl 3-(2-fluoro-4-{({4'-[(4-hydroxy-1-oxidotetrahydro-2H-thiopyran-4-yl)methoxy]-2',6'-dimethylbiphenyl-3-yl}methyl)[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoate

Produkt 1

HCID 59434131ethyl 3-{2-fluoro-4-[({4'-[(4-hydroxy-1-oxidotetrahydro-2H-thiopyran-4-yl)methoxy]-2',6'-dimethylbiphenyl-3-yl}methyl)amino]phenyl}propanoateAusbeute 50,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of ethyl 3-(2-fluoro-4-{({4′-[(4-hydroxytetrahydro-2H-thiopyran-4-yl)methoxy]-2′,6′-dimethylbiphenyl-3-yl}methyl) [(2-nitrophenyl)sulfonyl]amino}phenyl)propanoate (2.24 g, 3.04 mmol) in ethyl acetate (15 mL) was added m-chloroperbenzoic acid (70%, 0.46 g, 1.88 mmol) under stirring at 0° C., and the mixture was stirred at room temperature for 3 days. The reaction mixture was washed with 1 M aqueous sodium hydroxide solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=9/1-ethyl acetate-ethyl acetate/methanol=17/3) to give ethyl 3-(2-fluoro-4-{({4′-[(4-hydroxy-1-oxidotetrahydro-2H-thiopyran-4-yl)methoxy]-2′,6′-dimethylbiphenyl-3-yl}methyl)[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoate (1.36 g, yield 60%) as a colorless amorphous powder. To a solution of the obtained ethyl 3-(2-fluoro-4-{({4′-[(4-hydroxy-1-oxidotetrahydro-2H-thiopyran-4-yl)methoxy]-2′,6′-dimethylbiphenyl-3-yl}methyl)[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoate (1.36 g, 1.81 mmol) and mercaptoacetic acid (0.38 mL, 5.43 mmol) in N,N-dimethylformamide (10 mL) was added lithium hydroxide monohydrate (0.46 g, 10.86 mmol) under stirring at room temperature, and the mixture was stirred at the same temperature for 3 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogencarbonate and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=9/1-ethyl acetate) to give the title compound (0.52 g, yield 50%) as a colorless oil.

Aufarbeitung

  1. stirringthe mixture was stirred at the same temperature for 3 hr
  2. washwashed with saturated aqueous sodium hydrogencarbonate and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=9/1-ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-d7b016c54a4f44269033270f83ab7064
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07786165B2

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