2,6-Dichloropyridine → 2-Chloro-6-(1-cyclopropylmethyl-piperidin-4-yloxy)-pyridine

HRID 1822004

Reaktionsgleichung

Reaktionsgleichung von HRID 1822004
[H-].[Na+].[CH:3]1([CH2:6][N:7]2[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9][CH2:8]2)[CH2:5][CH2:4]1.[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17](Cl)[N:16]=1>CN(C=O)C>[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:13][CH:10]2[CH2:11][CH2:12][N:7]([CH2:6][CH:3]3[CH2:4][CH2:5]3)[CH2:8][CH2:9]2)[N:16]=1

Komponenten

5

Edukt 3

HCID 169892,6-DichloropyridineHCID 24758Sodium hydrideHCID 214287521-(Cyclopropylmethyl)piperidin-4-ol

Produkt 1

HCID 578937202-Chloro-6-(1-cyclopropylmethyl-piperidin-4-yloxy)-pyridineAusbeute 61 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Add NaH (60% dispersion in oil, 130 mg, 3.25 mmol) to a solution of 1-cyclopropylmethyl-piperidin-4-ol (preparation 11, 458 mg, 2.95 mmol) in DMF (8 mL) and stir for 20 min. Then add 2,6-dichloropyridine to the mixture and heat at 120° C. overnight. Quench the reaction with saturated NaHCO3, extract with methylene dichloride three times. Combine the organic layers, wash with saturated NaCl solution, dry over Na2SO4, filter and concentrate to give a residue. Chromatography (silica gel) eluting with 4% 2M NH3-methanol in methylene dichloride provides 480 mg (61%) of the title compound: mass spectrum (ion spray): m/z=267.2 (M+1); 1H NMR (CDCl3, ppm): 7.39 (t, 1H), 6.75 (d, 1H), 6.52 (d, 1H), 4.96 (m, 1H), 2.75 (m, 2H), 2.30 (m, 2H), 2.19 (d, 2H), 1.97 (m, 2H), 1.75 (m, 2H), 0.76 (m, 1H), 0.43 (m, 2H), 0.00 (m, 2H).

Aufarbeitung

  1. customQuench
  2. customthe reaction with saturated NaHCO3
  3. extractionextract with methylene dichloride three times
  4. washCombine the organic layers, wash with saturated NaCl solution
  5. dry with materialdry over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate
  8. customto give a residue
  9. washChromatography (silica gel) eluting with 4% 2M NH3-methanol in methylene dichloride

Quellen und Nachweise

ORD-Eintrag
ord-9cef1e8696f9412d89afe1c9b59298c5
Quelldatensatz
uspto-grants-2009_10
Patentnummer
US07608629B2

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