Sodium hydride → HCID 58293746, Verbindung

HRID 908384

Reaktionsgleichung

Reaktionsgleichung von HRID 908384
[H-].[Na+].[Br:3][C:4]1[C:5]([CH3:9])=[N:6][NH:7][CH:8]=1.CS(O[CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)(=O)=O>CN(C=O)C>[Br:3][C:4]1[CH:8]=[N:7][N:6]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[C:5]=1[CH3:9].[Br:3][C:4]1[C:5]([CH3:9])=[N:6][N:7]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[CH:8]=1

Komponenten

6

Edukt 3

HCID 24758Sodium hydrideHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidineHCID 178434489HCID 178434489, Verbindung

Produkt 2

HCID 58293746HCID 58293746, VerbindungHCID 59392614HCID 59392614, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Sodium hydride (60% dispersion in mineral oil, 11.53 g) was added portionwise to a stirred solution of 4-bromo-3-methyl-1H-pyrazole (42.2 g) dissolved in DMF (600 ml) over a period of 15 minutes at 0° C. under nitrogen. The resulting slurry was stirred at 0° C. for 1 hour. Then tert-butyl 4-methylsulphonyloxypiperidine-1-carboxylate (73.2 g) was added and the mixture was stirred 1 hour at room temperature then heated to 90° C. overnight. The reaction mixture was then allowed to stir at room temperature over a period of 2 days, quenched with water (2 ml), concentrated to dryness, diluted with ethyl acetate (1500 ml), washed with water (2×1000 ml), brine (1000 ml), dried over magnesium sulfate and concentrated to afford the crude product. A purification by flash chromatography on silica gel eluting with 20% ethyl acetate in petroleum ether afforded tert-butyl 4-(4-bromo-5-methyl-pyrazol-1-yl)piperidine-1-carboxylate (22.5 g) (NMR Spectrum: (DMSOd6) 1.42 (s, 9H), 1.72-1.86 (m, 4H), 2.28 (s, 3H), 2.91 (bs, 2H), 3.96-4.13 (m, 2H), 4.34-4.43 (m, 1H), 7.50 (s, 1H); Mass spectrum: M−tBu: 288,290), and tert-butyl 4-(4-bromo-3-methyl-pyrazol-1-yl)piperidine-1-carboxylate (28.7 g) (NMR Spectrum (DMSOd6): 1.44 (s, 9H), 1.70 (dd, 1H), 1.75 (dd, 1H), 1.91-1.99 (m, 2H), 2.11 (s, 3H), 2.87 (bs, 2H), 4.95-4.10 (m, 2H), 4.21-4.30 (m, 1H), 7.95 (s, 1H); Mass spectrum: M−tBu: 288,290).

Aufarbeitung

  1. stirringthe mixture was stirred 1 hour at room temperature
  2. temperaturethen heated to 90° C. overnight
  3. stirringto stir at room temperature over a period of 2 days
  4. customquenched with water (2 ml)
  5. concentrationconcentrated to dryness
  6. additiondiluted with ethyl acetate (1500 ml)
  7. washwashed with water (2×1000 ml), brine (1000 ml)
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. customto afford the crude product
  11. customA purification by flash chromatography on silica gel eluting with 20% ethyl acetate in petroleum ether

Quellen und Nachweise

ORD-Eintrag
ord-827d3c024ba84dd2a2ee3ef281c4c78d
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08017611B2

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