Potassium Carbonate → 6-[4-(3-Hydroxy-propyl)-phenoxy]-nicotinamide

HRID 130712

Reaktionsgleichung

Reaktionsgleichung von HRID 130712
C(=O)([O-])[O-].[K+].[K+].[OH:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][CH2:16][OH:17])=[CH:10][CH:9]=1.Cl[C:19]1[CH:27]=[CH:26][C:22]([C:23]([NH2:25])=[O:24])=[CH:21][N:20]=1.CC(N(C)C)=O>[OH-].[Na+].C(CC(C)(C)C)(C)C>[OH:17][CH2:16][CH2:15][CH2:14][C:11]1[CH:10]=[CH:9][C:8]([O:7][C:19]2[CH:27]=[CH:26][C:22]([C:23]([NH2:25])=[O:24])=[CH:21][N:20]=2)=[CH:13][CH:12]=1

Komponenten

7

Edukt 4

HCID 11430Potassium CarbonateHCID 31374DimethylacetamideHCID 804566-ChloronicotinamideHCID 824523-(4-Hydroxyphenyl)propanol

Produkt 1

HCID 597304116-[4-(3-Hydroxy-propyl)-phenoxy]-nicotinamideAusbeute 87 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 109072,2,4-TrimethylpentaneLösungsmittelHCID 14798Sodium HydroxideLösungsmittel

Versuchsvorschrift

Add potassium carbonate (2.2821 g, 16.51 mmol) to a stirred solution of 3-(4-hydroxyphenyl)-1-propanol (1.0041 g, 6.598 mmol), 6-chloronicotinamide (1.0038 g, 6.411 mmol), dimethylacetamide (21 mL), and isooctane (3 mL). Equip the reaction setup with a Dean-Stark trap and heat the reaction to reflux under nitrogen for 6 h. Cool the reaction to room temperature and filter off the solids. Concentrate on a rotary evaporator to give the crude product. Take the crude product up in 1 N sodium hydroxide (250 mL), extract with ethyl acetate (4×100 mL), dry the extracts over magnesium sulfate, filter, and concentrate on a rotary evaporator to give the crude product. The crude product is purified by flash chromatography on silica gel eluting with 1.5% concentrated ammonium hydroxide/15% ethanol/chloroform to yield 1.5188 g (87%) of 6-[4-(3-hydroxy-propyl)-phenoxy]-nicotinamide: mass spectrum (ion spray): m/z=273.2 (M+1); 1H NMR (DMSO-d6): 8.61 (d, 1H), 8.24 (dd, 1H), 8.03 (s, 1H), 7.48 (s, 1H), 7.25 (d, 2H), 7.07-7.03 (m, 3H), 4.50 (t, 1H), 3.46-3.41 (m, 2H), 2.63 (t, 2H), 1.77-1.70 (m, 2H).

Aufarbeitung

  1. customEquip the reaction setup with a Dean-Stark trap
  2. temperatureheat
  3. customthe reaction
  4. temperatureto reflux under nitrogen for 6 h
  5. temperatureCool
  6. customthe reaction to room temperature
  7. filtrationfilter off the solids
  8. concentrationConcentrate on a rotary evaporator
  9. customto give the crude product
  10. extractionextract with ethyl acetate (4×100 mL)
  11. dry with materialdry the extracts over magnesium sulfate
  12. filtrationfilter
  13. concentrationconcentrate on a rotary evaporator
  14. customto give the crude product
  15. customThe crude product is purified by flash chromatography on silica gel eluting with 1.5% concentrated ammonium hydroxide/15% ethanol/chloroform

Quellen und Nachweise

ORD-Eintrag
ord-b01d153a0a8a4da7a3ca2c0c0e65f5ad
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07381719B2

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