Sodium Iodide → 5-(2-{4-[5-(4-Fluoro-phenyl)-4-methoxymethyl-oxazol-2-yl]-piperidin-1-yl}-ethyl)-2-methoxy-benzenesulfonamide

HRID 2288997Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2288997
[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][NH:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[CH2:19][O:20][CH3:21])=[CH:4][CH:3]=1.Cl[CH2:23][CH2:24][C:25]1[CH:26]=[CH:27][C:28]([O:35][CH3:36])=[C:29]([S:31]([NH2:34])(=[O:33])=[O:32])[CH:30]=1.[I-].[Na+].C(N(C(C)C)CC)(C)C>O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH:13]3[CH2:14][CH2:15][N:16]([CH2:23][CH2:24][C:25]4[CH:26]=[CH:27][C:28]([O:35][CH3:36])=[C:29]([S:31]([NH2:34])(=[O:32])=[O:33])[CH:30]=4)[CH2:17][CH2:18]3)=[N:10][C:9]=2[CH2:19][O:20][CH3:21])=[CH:4][CH:3]=1

Komponenten

6

Edukt 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 187004064-[5-(4-Fluoro-Phenyl)-4-Methoxymethyl-Oxazol-2-yl]-PiperidineHCID 187004435-(2-Chloroethyl)-2-methoxy-benzenesulfonamide

Produkt 1

HCID 187004405-(2-{4-[5-(4-Fluoro-phenyl)-4-methoxymethyl-oxazol-2-yl]-piperidin-1-yl}-ethyl)-2-methoxy-benzenesulfonamideAusbeute 40 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A solution of 4-[5-(4-fluoro-phenyl)-4-methoxymethyl-oxazol-2-yl]-piperidine (0.3 g; 1.03 mmol) in dry dioxane (7 ml) is treated with 5-(2-chloroethyl)-2-methoxy-benzenesulfonamide (0.52 g; 2.06 mmol), sodium iodide (0.31 g; 2.06 mmol) and diisopropylethylamine (0.72 ml; 4.12 mmol) and heated to 100 C. for 16 hours. The reaction mixture is partitioned between ethyl acetate (50 ml) and dilute sodium bicarbonate (20 ml). The aqueous phase is washed with ethyl acetate (20 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%) is followed by a second chromatography using a methanol/dichloromethane gradient (5%-15%). Crystallization from dichloromethane/ethyl acetate afforded the product as a white solid (0.20 g; 40%). HNMR (CDCl3): 7.72 (d, 1H, J=2.1 Hz), 7.62 (m, 2H), 7.35 (dd, 1H, J=8.6; 2.1 Hz), 7.13 (t, 21H, J=8.6 Hz), 6.96 (d, 1H, J=8.6 Hz), 5.64 (broad s, 2H), 4.44 (s, 2H), 3.97 (s, 3H), 3.44 (s, 3H), 2.96 (m, 2H), 2.80 (m, 1H), 2.75 (m, 2H), 2.53 (m, 2H), 2.10 (m, 4H), 1.90 (m, 2H). Mass spectrum: m/e calculated (MH+)=504; observed (MH+)=504.

Aufarbeitung

  1. temperatureheated to 100 C
  2. customThe reaction mixture is partitioned between ethyl acetate (50 ml) and dilute sodium bicarbonate (20 ml)
  3. washThe aqueous phase is washed with ethyl acetate (20 ml)
  4. washThe combined organic phases are washed with saturated brine (10 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to dryness
  7. customPurification by radial chromatography on silica gel using a methanol/ethyl acetate gradient (5%-20%)
  8. customCrystallization from dichloromethane/ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-15f4c31937b64230bc5d2a5da91c81f3
Quelldatensatz
uspto-grants-2000_07
Patentnummer
US06090825

Notizen zur Reaktion

Wird geladen…