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

HRID 2259674

Reaktionsgleichung

Reaktionsgleichung von HRID 2259674
[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). Analysis for C17H15F 2NO3.0.2 H2O: Calculated: C, 63.23; H, 4.81; N, 4.34 Found: C, 63.21; H, 4.74; N, 4.30

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-e76d340e689d4b8a82b8e7169283b91f
Quelldatensatz
uspto-grants-1995_12
Patentnummer
US05474999

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