Sodium hydride → 1-t-Butyloxycarbonyl-4-[(3-phenyl-2-propynyloxy)ethyl]piperidine

HRID 1655966

Reaktionsgleichung

Reaktionsgleichung von HRID 1655966
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([CH2:16][CH2:17][OH:18])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH:19]1[CH:24]=[CH:23][C:22]([C:25]#[C:26][CH2:27]Cl)=[CH:21][CH:20]=1>CN(C)C=O>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([CH2:16][CH2:17][O:18][CH2:27][C:26]#[C:25][C:22]2[CH:23]=[CH:24][CH:19]=[CH:20][CH:21]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 287343(3-Chloroprop-1-yn-1-yl)benzeneHCID 8541401-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidine

Produkt 1

HCID 538709501-t-Butyloxycarbonyl-4-[(3-phenyl-2-propynyloxy)ethyl]piperidineAusbeute 16 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Sodium hydride (0.912 g, 23 mmol, 60% oil disp.) which had been rinsed with hexanes (3×10 mL), and dry N,N-dimethylformamide (50 mL) were cooled to 0° C. with stirring under a nitrogen atmosphere. A solution of 1-t-butyloxycarbonyl-4-hydroxyethylpiperidine (4.3 g, 19 mmol) in dry DMF (15 mL) was added, and the mixture stirred for 1 hour. 3-Phenylpropargyl chloride (2.8 g, 19 mmol) was added, and the mixture was heated to reflux for 24 hours. After cooling, the solvent was removed by distillation under reduced pressure. The residue was dissolved in ethyl acetate and extracted with water (3×100 mL), brine (100 mL), dried (MgSO4), filtered, and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel, eluting with 5% ethyl acetate in hexanes, and concentrated under reduced pressure to yield 1-t-butyloxycarbonyl-4-[(3-phenyl-2-propynyloxy)ethyl]piperidine (1.02 g, 16%) as a dark oil. 1H NMR (300 MHz, CDCl3 /TMS, δ): 7.5(m,2H), 7.3(m,3H), 4.4(s,2H), 4.1(m,2H), 3.6(t,2H), 2.7(br t,2H), 1.8-1.1(m,16H). MSCI: 344 (MH+, base).

Aufarbeitung

  1. stirringthe mixture stirred for 1 hour
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 24 hours
  4. temperatureAfter cooling
  5. customthe solvent was removed by distillation under reduced pressure
  6. dissolutionThe residue was dissolved in ethyl acetate
  7. extractionextracted with water (3×100 mL), brine (100 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude product was purified by chromatography on silica gel
  12. washeluting with 5% ethyl acetate in hexanes
  13. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-450e5204bc9f4f7187bea0a53bbe1c6d
Quelldatensatz
uspto-grants-1993_10
Patentnummer
US05252586

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