Ammonium Chloride → 5-Fluoropyridine-2-carboxamide

HRID 228281

Reaktionsgleichung

Reaktionsgleichung von HRID 228281
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.O[N:12]1C(=O)CCC1=O.Cl.CN(C)CCCN=C=NCC.[Cl-].[NH4+]>C1COCC1.CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH2:12])=[O:10])=[N:6][CH:7]=1

Komponenten

7

Edukt 4

HCID 25517Ammonium ChlorideHCID 80170N-HydroxysuccinimideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27628765-fluoropyridine-2-carboxylic Acid

Produkt 1

HCID 219047545-Fluoropyridine-2-carboxamideAusbeute 80,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Take up 5-Fluoropyridine-2-carboxylic acid (3.82 g, 27.1 mmol) in THF (67.7 mL). Add N-hydroxysuccinimide (3.43 g, 29.8 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (5.71 g, 29.8 mmol). Add DMF (15 mL) to dissolve the gum formed. Stir for 3 hours at room temperature before adding ammonium chloride (2.17 g, 40.6 mmol). Bubble in ammonia gas for five minutes. Seal the reaction vessel and stir the reaction mixture overnight before concentrating. Take the solid up in water (150 mL) and extract with ethyl acetate (4×225 mL). Dry the organic layer over Na2SO4 filter and concentrate. Purify by flash chromatography eluting with 25% ethyl acetate, 1% (2.0 M NH3 in methanol) and 74% dichloromethane to give the title compound (3.06 g, 80.7%): TOF MS EI+ 140.0 (M)+, TOF MS EI+ 97.0 (M+H—CONH2)+, HRMS calcd for C6H5N2OF 140.0386, found 140.0394, time 3.41 min; HPLC [YMC-Pack Pro C-18 (150×4.6 nm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 5-95% over 19 min], tR=7.1 min, 100% purity.

Aufarbeitung

  1. customformed
  2. customBubble in ammonia gas for five minutes
  3. customSeal the reaction vessel
  4. stirringstir the reaction mixture overnight
  5. concentrationbefore concentrating
  6. extractionextract with ethyl acetate (4×225 mL)
  7. dry with materialDry the organic layer over Na2SO4
  8. filtrationfilter
  9. concentrationconcentrate
  10. customPurify by flash chromatography
  11. washeluting with 25% ethyl acetate, 1% (2.0 M NH3 in methanol) and 74% dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-22f38e3ab3e946249ec178457c80b203
Quelldatensatz
uspto-grants-2009_07
Patentnummer
US07560463B2

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