Thionyl Chloride → N-[4-(2-Pyridylsulfonyl)phenyl]-3,3-difluoro-2-hydroxy-2-difluoromethyl propionamide

HRID 2259704Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2259704
[F:1][CH:2]([F:11])[C:3]([CH:8]([F:10])[F:9])([OH:7])[C:4](O)=[O:5].S(Cl)(Cl)=O.[N:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[S:22]([C:25]1[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=1)(=[O:24])=[O:23].C(=O)(O)[O-].[Na+]>CC(N(C)C)=O.O>[N:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[S:22]([C:25]1[CH:31]=[CH:30][C:28]([NH:29][C:4](=[O:5])[C:3]([OH:7])([CH:8]([F:10])[F:9])[CH:2]([F:11])[F:1])=[CH:27][CH:26]=1)(=[O:23])=[O:24]

Komponenten

7

Edukt 4

HCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 105138504-(2-Pyridylsulfonyl)anilineHCID 222874542,2-Bis-difluoromethyl-2-hydroxyacetic acid

Produkt 1

HCID 21480114N-[4-(2-Pyridylsulfonyl)phenyl]-3,3-difluoro-2-hydroxy-2-difluoromethyl propionamideAusbeute 43 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
-10 °C

Versuchsvorschrift

To a solution of 2,2-bis-difluoromethyl-2-hydroxyacetic acid (0.5 g, 2.84 mmole) in dimethylacetamide (10 ml) at -10° C. was added thionyl chloride (0.34 g, 2.84 mmol) dropwise. The resulting solution was stirred at -10° C. for approximately 30 min. 4-(2-Pyridylsulfonyl)aniline (0.58 g, 2.5 mmol) was added and the reaction mixture was stirred overnight at room temperature. The reaction mixture was then poured into water, and sodium bicarbonate solution was added to give a pH of 7-7.5. A brown colored precipitate was formed. The solid was filtered, washed with water, and dried. Crystallization and decoloration (charcoal) from ethyl acetate/methanol/hexane gave the title compound (0.42 g, 43%) as off-white leaves; mp 200°-202° C. 1H-NMR(300 MHz, d6 -DMSO): 6.45 (t, J=54.09 Hz, 2H, HCF2), 7.68(t, J=6.24 Hz, 1H, ArH), 7.92-8.03 (m, 5H, ArH, OH), 8.11-8.21 (m, 2H, ArH), 8.68 (d, J=4.47 Hz, 1H, ArH), 10.54 (s, 1H, NH). MS(CI,CH4): 393 (M+1, 100%). Analysis for C15H12F4N2O4S: Calculated: C, 45.92; H, 3.08; N, 7.14 Found: C, 45.89; H, 3.17; N, 7.12

Aufarbeitung

  1. stirringthe reaction mixture was stirred overnight at room temperature
  2. additionwas added
  3. customto give a pH of 7-7.5
  4. customA brown colored precipitate was formed
  5. filtrationThe solid was filtered
  6. washwashed with water
  7. customdried
  8. customCrystallization and decoloration (charcoal) from ethyl acetate/methanol/hexane

Quellen und Nachweise

ORD-Eintrag
ord-121a4800f40245ae87f854d104e1ef14
Quelldatensatz
uspto-grants-1995_12
Patentnummer
US05474999

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