Sodium hydride → 5-Fluoro-2-(1-methyl-3-pyrrolidinyloxy)benzamide

HRID 364375Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 364375
[H-].[Na+].[F:3][C:4]1[CH:5]=[CH:6][C:7]([OH:13])=[C:8]([CH:12]=1)[C:9]([NH2:11])=[O:10].CS(O[CH:19]1[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20]1)(=O)=O>CN(C)C=O>[F:3][C:4]1[CH:5]=[CH:6][C:7]([O:13][CH:19]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20]2)=[C:8]([CH:12]=1)[C:9]([NH2:11])=[O:10]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 137262825-Fluoro-2-hydroxybenzamideHCID 219142741-Methylpyrrolidin-3-yl methanesulfonate

Produkt 1

HCID 137262885-Fluoro-2-(1-methyl-3-pyrrolidinyloxy)benzamideAusbeute 42 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a suspension of 0.44 g (60% in oil, 0.011 mole) of sodium hydride in 10 ml of dimethylformamide was added 1.55 g (0.01 mole) of 5-fluoro-2-hydroxybenzamide in 10 ml of dimethylformamide under nitrogen atmosphere at room temperature. The reaction mixture was heated to 60° C. and 1.80 g (0.01 mole) of 1-methyl-3-pyrrolidinol methane sulfonate (ester) was added. The reaction mixture was then heated to 100° C. for 18 hr. The dimethylformamide was removed by rotary evaporation at 70° C., 0.5 mm Hg. The residue was taken up in 200 ml of methylene chloride, washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water. The organic phase was extracted with 2×50 ml of 1N hydrochloric acid. The combined aqueous extracts were washed with 50 ml of methylene chloride, made basic with concentrated sodium hydroxide and extracted into 2×50 ml of methylene chloride. The combined organic extracts were dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residual oil was crystallized from hexane to give 1.0 g of off-white crystals, m.p. 90°-93° C.

Aufarbeitung

  1. temperatureThe reaction mixture was then heated to 100° C. for 18 hr
  2. customThe dimethylformamide was removed by rotary evaporation at 70° C.
  3. washwashed with 2×50 ml of 1N sodium hydroxide and 50 ml of water
  4. extractionThe organic phase was extracted with 2×50 ml of 1N hydrochloric acid
  5. washThe combined aqueous extracts were washed with 50 ml of methylene chloride
  6. extractionextracted into 2×50 ml of methylene chloride
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated by rotary evaporation
  10. customThe residual oil was crystallized from hexane

Quellen und Nachweise

ORD-Eintrag
ord-809f71f3afa04e7a8b1de75b6cb7bbc7
Quelldatensatz
uspto-grants-1986_08
Patentnummer
US04604388

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