Methane → N-[4-(Phenylcarbonyl)phenyl]-3,3,-difluoro-2-hydroxy-2-methylpropanamide

HRID 327183

Reaktionsgleichung

Reaktionsgleichung von HRID 327183
[OH:1][C:2]([CH:7]([F:9])[F:8])([CH3:6])[C:3](O)=[O:4].S(Cl)(Cl)=O.[NH2:14][C:15]1[CH:28]=[CH:27][C:18]([C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:20])=[CH:17][CH:16]=1.Cl.C>CC(N(C)C)=O>[C:21]1([C:19]([C:18]2[CH:17]=[CH:16][C:15]([NH:14][C:3](=[O:4])[C:2]([OH:1])([CH3:6])[CH:7]([F:9])[F:8])=[CH:28][CH:27]=2)=[O:20])[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Komponenten

7

Edukt 5

HCID 297MethaneHCID 313Hydrochloric AcidHCID 143464-AminobenzophenoneHCID 24386Thionyl ChlorideHCID 147860322-(Difluoromethyl)-2-hydroxypropionic acid

Produkt 1

HCID 21480151N-[4-(Phenylcarbonyl)phenyl]-3,3,-difluoro-2-hydroxy-2-methylpropanamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
-10 °C

Versuchsvorschrift

A solution of 2-hydroxy-2-difluoromethylpropionic acid (1.07 g, 7.65 mmol) in dry dimethylacetamide (15 ml) was stirred under a nitrogen atmosphere at -10° C. Thionyl chloride (0.91 g, 7.65 mmol) was added and the resulting mixture was allowed to stir at -10° C. for 1 hour. 4-Aminobenzophenone (1.0 g, 5.1 mmol) was then added and the reaction mixture was stirred at -10° C. for a further 15 mins. The solution was then allowed to warm to room temperature where it was stirred overnight. The reaction mixture was poured into hydrochloric acid solution (1M) and extracted with ethyl acetate. The combined ethyl acetate fractions were washed with water and brine. After drying (Na2SO4) and decolorization (Charcoal) the solution was evaporated in vacuo. A off-white foam was obtained which was triturated with hexane/ethyl acetate. The crude product was filtered through a short silica gel column with chloroform and crystallized from chloroform/hexane to give the title tertiary carbinol (0.89 g, 55%) as shiny, buff-colored crystals; mp=123°-124° C. 1H--NMR (300 MHz, d6 --DMSO): 1.45 (s, 3H, CH3), 6.17 (t, J=55 Hz, 1H, CHF2), 6.77 (s, 1H, OH), 7.56 (t, 2H, ArH), 7.65-7.76 (m, 5H, ArH), 7.96 (d, J=8.7 Hz, 2H, ArH), 10.19 (s, 1H, NH). MS (CI, CH4): 320(M+1, 100).

Aufarbeitung

  1. stirringthe reaction mixture was stirred at -10° C. for a further 15 mins
  2. temperatureto warm to room temperature where it
  3. stirringwas stirred overnight
  4. extractionextracted with ethyl acetate
  5. washThe combined ethyl acetate fractions were washed with water and brine
  6. dry with materialAfter drying (Na2SO4) and decolorization (Charcoal) the solution
  7. customwas evaporated in vacuo
  8. customA off-white foam was obtained which
  9. customwas triturated with hexane/ethyl acetate
  10. filtrationThe crude product was filtered through a short silica gel column with chloroform
  11. customcrystallized from chloroform/hexane
  12. customto give the title tertiary carbinol (0.89 g, 55%) as shiny, buff-colored crystals

Quellen und Nachweise

ORD-Eintrag
ord-c8f678247e01490280a922a3f637af7e
Quelldatensatz
uspto-grants-1993_12
Patentnummer
US05272163

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