Hydrogen Bromide → 2-Bromo-3-[2-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]-5-pyridyl]propionic acid methyl ester

HRID 2395697Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2395697
N[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH2:9][CH2:10][C:11]2[N:12]=[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[O:14][C:15]=2[CH3:16])=[N:6][CH:7]=1.[BrH:23].N([O-])=O.[Na+].[C:28]([O:32][CH3:33])(=[O:31])[CH:29]=[CH2:30]>O.CC(C)=O>[CH3:33][O:32][C:28](=[O:31])[CH:29]([Br:23])[CH2:30][C:2]1[CH:3]=[CH:4][C:5]([O:8][CH2:9][CH2:10][C:11]2[N:12]=[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[O:14][C:15]=2[CH3:16])=[N:6][CH:7]=1

Komponenten

7

Edukt 4

HCID 260Hydrogen BromideHCID 7294Methyl AcrylateHCID 110877225-Amino-2-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]pyridineHCID 23668193Sodium Nitrite

Produkt 1

HCID 536876832-Bromo-3-[2-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]-5-pyridyl]propionic acid methyl esterAusbeute 68 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 180AcetoneLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
10 °C

Versuchsvorschrift

To a mixture of 5-amino-2-[2-(5-methyl-2-phenyl-4-oxazolyl) ethoxy]pyridine (4.5 g), aqueous HBr (47%, 7.1 ml) and acetone (70 ml) was added an aqueous solution of sodium nitrite (NaNO2) (1.17 g) in water (5 ml) dropwise at a temperature of under 10° C. After stirring at 10° C. for 30 minutes, the temperature was increased to 30° C., and methyl acrylate (8.3 ml) was added. Then, cuprous oxide (Cu2O) (0.1 g) was added little by little, and the mixture was vigorously stirred. The reaction mixture was further stirred at 40° to 45° C. for 1 more hour and then concentrated under reduced pressure. After alkalinization with concentrated aqueous ammonia, the residue was extracted with ethyl acetate. After the ethyl acetate layer was washed with water and dried (MgSO4), the solvent was distilled off under reduced pressure. The residual oily substance was subjected to silica gel chromatography. From the fraction eluted with ethyl acetate-hexane (2:1, v/v), 2-bromo-3-[2-[2-(5-methyl-2-phenyl-4-oxazolyl]ethoxy]-5-pyridyl]propionic acid methyl ester (4.7 g, 68%) was obtained. NMR (δ ppm in CDCl3): 2.34 (3H, s), 2.98 (2H, t, J=6.7 Hz), 3.16 (1H, dd, J=7.0 & 14.5 Hz), 3.37 (1H, dd, J=8.0 & 14.5 Hz), 3.74 (3H, s), 4.31 (1H, dd, J=8.0 & 7.0 Hz), 4.55 (2H, t, J=6.7 Hz), 6.67 (1H, d, J=8.6 Hz), 7.35-7.50 (4H, m), 7.90-8.05 (3H, m)

Aufarbeitung

  1. temperaturethe temperature was increased to 30° C.
  2. stirringwas vigorously stirred
  3. stirringThe reaction mixture was further stirred at 40° to 45° C. for 1 more hour
  4. concentrationconcentrated under reduced pressure
  5. extractionAfter alkalinization with concentrated aqueous ammonia, the residue was extracted with ethyl acetate
  6. washAfter the ethyl acetate layer was washed with water
  7. dry with materialdried (MgSO4)
  8. distillationthe solvent was distilled off under reduced pressure
  9. washFrom the fraction eluted with ethyl acetate-hexane (2:1

Quellen und Nachweise

ORD-Eintrag
ord-5305de6ee043473c9066d6dbef738417
Quelldatensatz
uspto-grants-1996_02
Patentnummer
US05489602

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