Dimethylformamide → 6-Bromo-2-chloro-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile

HRID 17437

Reaktionsgleichung

Reaktionsgleichung von HRID 17437
[NH2:1][C:2]1[C:9](O)=[C:8]([F:11])[C:7]([Br:12])=[C:6]([CH3:13])[C:3]=1C#N.C(=S)(OCC)[S-].[K+].[CH3:21][N:22](C)[CH:23]=[O:24].S(Cl)([Cl:28])=O>N1C=CC=CC=1>[Br:12][C:7]1[C:8]([F:11])=[C:9]2[O:24][C:23]([Cl:28])=[N:22][C:21]2=[C:3]([C:2]#[N:1])[C:6]=1[CH3:13]

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 2735045Potassium ethylxanthate2×HCID 860975142-Amino-5-bromo-4-fluoro-3-hydroxy-6-methylbenzonitrile2×

Produkt 1

HCID 685849876-Bromo-2-chloro-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrileAusbeute 55 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1049PyridineLösungsmittel2×

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

2-Amino-5-bromo-4-fluoro-3-hydroxy-6-methylbenzonitrile (I-75) (1.54 g, 6.28 mmol) was dissolved in pyridine (80 ml), then potassium O-ethyl dithiocarbonate (3.10 g, 19.3 mmol) was added, followed by heating under reflux for 3 hours. The solvent was evaporated away under reduced pressure, then ethyl acetate and diluted hydrochloric acid were added for liquid-liquid separation of the organic layer. After washing with water and saturated brine and drying over anhydrous sodium sulfate, the solvent was evaporated away under reduced pressure. Again using 2-amino-5-bromo-4-fluoro-3-hydroxy-6-methylbenzonitrile (I-75) (1.45 g, 5.92 mmol), pyridine (75 ml) and potassium O-ethyl dithiocarbonate (2.90 g, 18.1 mmol), the same reaction was carried out, and the resulting residues were combined, dissolved in thionyl chloride (70 ml). N,N-dimethylformamide (0.70 ml) was added, followed by stirring at an external temperature of about 70° C. for 1 hour, then the reaction liquid was concentrated under reduced pressure. Dichloromethane and aqueous sodium hydrogencarbonate solution were added, and the organic layer was separated. After extraction with dichloromethane, the organic layers were combined, and dried over anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified by silica gel column chromatography (dichloromethane) to obtain the entitled compound (1.93 g, 55%) as a brown solid.

Aufarbeitung

  1. temperatureby heating
  2. temperatureunder reflux for 3 hours
  3. customThe solvent was evaporated away under reduced pressure
  4. additionethyl acetate and diluted hydrochloric acid were added for liquid-liquid separation of the organic layer
  5. washAfter washing with water and saturated brine
  6. dry with materialdrying over anhydrous sodium sulfate
  7. customthe solvent was evaporated away under reduced pressure
  8. customthe reaction liquid
  9. concentrationwas concentrated under reduced pressure
  10. additionDichloromethane and aqueous sodium hydrogencarbonate solution were added
  11. customthe organic layer was separated
  12. extractionAfter extraction with dichloromethane
  13. dry with materialdried over anhydrous sodium sulfate
  14. customThe solvent was evaporated away under reduced pressure
  15. customthe resulting residue was purified by silica gel column chromatography (dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-c08ea25674854155a01a356cdc40cea0
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07737166B2

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