Methyl iodide → 1-{4-[5-(4-Fluoro-phenyl)-4-Methoxymethyl-Oxazol-2-yl]-Piperidin-1-yl}-Ethanone

HRID 2288986Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2288986
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH:13]3[CH2:18][CH2:17][N:16]([C:19](=[O:21])[CH3:20])[CH2:15][CH2:14]3)=[N:10][C:9]=2[CH2:22][OH:23])=[CH:4][CH:3]=1.[H-].[Na+].[CH3:26]I>O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH:13]3[CH2:18][CH2:17][N:16]([C:19](=[O:21])[CH3:20])[CH2:15][CH2:14]3)=[N:10][C:9]=2[CH2:22][O:23][CH3:26])=[CH:4][CH:3]=1

Komponenten

5

Edukt 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 187004631-(4-[5-(4-Fluoro-phenyl)-4-hydroxymethyl-oxazol-2-yl]-piperidin-1-yl)-ethanone

Produkt 1

HCID 187004251-{4-[5-(4-Fluoro-phenyl)-4-Methoxymethyl-Oxazol-2-yl]-Piperidin-1-yl}-EthanoneAusbeute 75,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A solution of 1-{4-[5-(4-fluoro-phenyl)-4-hydroxymethyl-oxazol-2-yl]-piperidin-1-yl}-ethanone (1.0 g; 3.14 mmol) in dry tetrahydrofuran (12 ml) is treated with sodium hydride (0.16 g; 4.09 mmol) in small portions. After 5 minutes, it is added methyl iodide (0.31 ml; 5.02 mmol) and the mixture is stirred for 45 minutes. The reaction is partitioned between ethyl acetate (40 ml) and water (15 ml). The aqueous phase is washed with ethyl acetate (15 ml). The combined organic phases are washed with saturated brine (10 ml), dried over sodium sulfate and concentrated to dryness. Purification by radial chromatography on silica gel using a methanol/ethyl acetate gradient (5%-20%) afforded the product as a light yellow oil (0.79 g; 75%). HNMR (CDCl3): 7.53 (m, 2H), 7.04 (t, 2H, J=8.7 Hz), 4.43 (m, 1H), 4.37 (s, 2H), 3.80 (m, 1H), 3.37 (s, 3H), 3.15 (m, 1H), 3.0 (ttt, 1H, J=10.8; 4.1 Hz), 2.79 (m, 1H), 2.04 (m, 2H), 2.02 (s, 3H), 1.77 (m, 2H). Mass spectrum: m/e calculated (MNa+)=355; observed (MNA+)=355.

Aufarbeitung

  1. customThe reaction is partitioned between ethyl acetate (40 ml) and water (15 ml)
  2. washThe aqueous phase is washed with ethyl acetate (15 ml)
  3. washThe combined organic phases are washed with saturated brine (10 ml)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated to dryness
  6. customPurification by radial chromatography on silica gel using a methanol/ethyl acetate gradient (5%-20%)

Quellen und Nachweise

ORD-Eintrag
ord-843d8fb87f1d419c823fdf0fadf5d83a
Quelldatensatz
uspto-grants-2000_07
Patentnummer
US06090825

Notizen zur Reaktion

Wird geladen…