Water → 1-(4-[5-(4-Fluoro-phenyl)-4-hydroxymethyl-oxazol-2-yl]-piperidin-1-yl)-ethanone

HRID 2288964Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2288964
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:24])[CH:9]([NH:12][C:13]([CH:15]2[CH2:20][CH2:19][N:18]([C:21](=[O:23])[CH3:22])[CH2:17][CH2:16]2)=O)[CH2:10][OH:11])=[CH:4][CH:3]=1.N1C=CC=CC=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.O>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:24][C:13]([CH:15]3[CH2:16][CH2:17][N:18]([C:21](=[O:23])[CH3:22])[CH2:19][CH2:20]3)=[N:12][C:9]=2[CH2:10][OH:11])=[CH:6][CH:7]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 1049PyridineHCID 9845Trifluoroacetic anhydrideHCID 537430491-Acetyl-piperidine-4-carboxylic acid [2-(4-fluoro-phenyl)-1-hydroxymethyl-2-oxo-ethyl]-amide

Produkt 1

HCID 187004631-(4-[5-(4-Fluoro-phenyl)-4-hydroxymethyl-oxazol-2-yl]-piperidin-1-yl)-ethanone

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
-10 °C

Versuchsvorschrift

To a slurry of 1-Acetyl-piperidine-4-carboxylic acid [2-(4-fluoro-phenyl)-1-hydroxymethyl-2-oxo-ethyl]-amide, prepared as in Part B, (100 g, 0.30 mol) and pyridine (100 mL, 1.20 mole) in dichloromethane (900 mL) at -40° C. is added trifluoroacetic anhydride (200 mL, 1.40 mole) over 1.5 hrs. The reaction is allowed to warm to -10° C. over 2 hrs and stirred at -10° C. for 1.5 hrs. Water (200 mL) is added, keeping the temperature at 0°--5° C. The layers are separated and the dichloromethane is washed with water (6×400 mL), dried (MgSO4) and concentrated to a yellow oil. The oil is taken up in methanol (600 mL) and silica gel (100 g) is added and the mixture stirred at 20° C. for 16 hrs. The silica gel is removed by filtration, rinsed with methanol (400 mL) and the filtrate is concentrated. Ether (500 mL) is added to the residue and stirred for 2 hrs and the resulting solid is filtered to afford 1-(4-[5-(4-fluoro-phenyl)-4-hydroxymethyl-oxazol-2-yl]-piperidin-1-yl)-ethanone as a pale yellow solid.

Aufarbeitung

  1. customat 0°--5° C
  2. customThe layers are separated
  3. washthe dichloromethane is washed with water (6×400 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated to a yellow oil
  6. additionsilica gel (100 g) is added
  7. stirringthe mixture stirred at 20° C. for 16 hrs
  8. customThe silica gel is removed by filtration
  9. washrinsed with methanol (400 mL)
  10. concentrationthe filtrate is concentrated
  11. additionEther (500 mL) is added to the residue
  12. stirringstirred for 2 hrs
  13. filtrationthe resulting solid is filtered

Quellen und Nachweise

ORD-Eintrag
ord-e082142f37ea41928ddf919ffda94e8b
Quelldatensatz
uspto-grants-2000_07
Patentnummer
US06090825

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