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

HRID 2292960Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2292960
[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.[C:16]1([S:22]([C:25]2[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=2)(=[O:24])=[O:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)(O)[O-].[Na+]>CC(N(C)C)=O.O>[C:16]1([S:22]([C:25]2[CH:26]=[CH:27][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:30][CH:31]=2)(=[O:23])=[O:24])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Komponenten

7

Edukt 4

HCID 24386Thionyl ChlorideHCID 5166664-(Phenylsulfonyl)anilineHCID 516892Sodium BicarbonateHCID 222874542,2-Bis-difluoromethyl-2-hydroxyacetic acid

Produkt 1

HCID 21480121N-[4-(Phenylsulfonyl)phenyl]-3,3-difluoro-2-hydroxy-2-difluoromethyl propionamideAusbeute 57,2 %

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 mmoles) in dimethylacetamide (10 ml) at -10° C. was added thionyl chloride (0.34 g, 2.84 mmoles) dropwise. The resulting solution was stirred at -10° C. for approximately 30 mins. 4-(Phenylsulfonyl) aniline (0.58 g, 2.5 mmoles) was added and the reaction mixture was stirred overnight at room temperature. The reaction mixture was then poured into water, sodium bicarbonate solution added to give a pH of 7 and extracted with ethyl acetate. The ethyl acetate extracts were combined, washed with water, brine, dried (Na2SO4), decolorized (charcoal), and evaporated. The crude solid was dissolved in ether, clarified by filtration, and evaporated. Crystallization from methanol/water gave the title compound (0.56 g, 57%) as white, silky needles; mp 105°-108° C. 1H-NMR (300 H B z, d6 -DMSO) 6.44 (t, J=53.94 Hz, 2H, HCF2), 7.58-7.68(m, 3H, ArH), 7.92-8.01 (m, 7H, ArH, OH), 10.51 (s, 1H, NH). MS(CI,CH4): 392 (M+1, 100%).

Aufarbeitung

  1. stirringthe reaction mixture was stirred overnight at room temperature
  2. additionadded
  3. customto give a pH of 7
  4. extractionextracted with ethyl acetate
  5. washwashed with water, brine
  6. dry with materialdried (Na2SO4)
  7. customevaporated
  8. dissolutionThe crude solid was dissolved in ether
  9. filtrationclarified by filtration
  10. customevaporated
  11. customCrystallization from methanol/water

Quellen und Nachweise

ORD-Eintrag
ord-6e32081c80f14d0a95ffefa3ed14113c
Quelldatensatz
uspto-grants-1997_11
Patentnummer
US05684198

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