Hydrochloric Acid → 3-(4-{4-[2-Dimethylcarbamoyl-2-(toluene-4-sulfonylamino)-ethyl]-phenoxy}-phenyl)-propionic acid methyl ester

HRID 748996Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 748996
Cl.Cl.[CH3:3][O:4][C:5](=[O:29])[CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH:22]([NH2:28])[C:23](=[O:27])[N:24]([CH3:26])[CH3:25])=[CH:17][CH:16]=2)=[CH:10][CH:9]=1.CCN(C(C)C)C(C)C.[C:39]1([CH3:49])[CH:44]=[CH:43][C:42]([S:45](Cl)(=[O:47])=[O:46])=[CH:41][CH:40]=1>C(Cl)Cl.C(O)(=O)C.C(OCC)(=O)C>[CH3:3][O:4][C:5](=[O:29])[CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH:22]([C:23](=[O:27])[N:24]([CH3:25])[CH3:26])[NH:28][S:45]([C:42]3[CH:43]=[CH:44][C:39]([CH3:49])=[CH:40][CH:41]=3)(=[O:47])=[O:46])=[CH:17][CH:16]=2)=[CH:10][CH:9]=1

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 73974-Toluenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 691134593-{4-[4-(2-Amino-2-dimethylcarbamoyl-ethyl)-phenoxy]-phenyl}-propionic acid methyl ester hydrochloric acid salt

Produkt 1

HCID 691137573-(4-{4-[2-Dimethylcarbamoyl-2-(toluene-4-sulfonylamino)-ethyl]-phenoxy}-phenyl)-propionic acid methyl esterAusbeute 56,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 176Acetic AcidLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
2.5 °C

Versuchsvorschrift

Hydrochloride compound 23 (1.5 g, 3.69 mmol) was dissolved in CH2Cl2 (50 mL) and cooled to 0-5° C. N,N′-Diisopropylethylamine (1.28 mL, 7.74 mmol) was added to the above solution followed by addition of p-toluenesulfonyl chloride (0.58 g, 3.06 mmol) in small portions. The reaction mixture was then warmed up to room temperature and stirred overnight. The solvent was removed under reduced pressure and the residual oil was taken up in EtOAc (75 mL). The organic layer was washed with 2.0 M HCl (1×10 mL), water (1×50 mL), and brine (2×50 mL). The resulting EtOAc layer was dried and concentrated under reduced pressure to yield oil. Flash chromatography (hexanes:ethyl acetate—3:2 containing 1% acetic acid) yielded the desired sulfonamide 24 (0.9 g, 47%). 1H NMR (400 MHz, DMSO-d6): 7.54 (d, J=8.4 Hz, 2H), 7.29 (d, J=8.0 Hz, 2H), 7.22 (d, J=8.8 Hz, 2H), 7.10 (d, J=8.4 Hz, 2H), 6.86 (d, J=8.8 Hz, 2H), 6.82 (d, J=8.4 Hz, 2H), 4.39 (m, 1H), 3.58 (s, 3H), 2.72-2.92 (m, 4H), 2.69 (s, 3H), 2.57-2.64 (m, 4H), 2.47 (s, 3H), 2.35 (s, 3H).

Aufarbeitung

  1. temperatureThe reaction mixture was then warmed up to room temperature
  2. customThe solvent was removed under reduced pressure
  3. washThe organic layer was washed with 2.0 M HCl (1×10 mL), water (1×50 mL), and brine (2×50 mL)
  4. dry with materialThe resulting EtOAc layer was dried
  5. concentrationconcentrated under reduced pressure
  6. customto yield oil

Quellen und Nachweise

ORD-Eintrag
ord-9c6840aae85c45ea8bf1d34cf83be389
Quelldatensatz
uspto-grants-2008_07
Patentnummer
US07399786B2

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