Hydrochloric Acid → Methyl 2-(2,4-difluorophenyl)isonicotinate hydrochloride

HRID 1963169Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1963169
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[F:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].Cl>CO.CC(OC)(C)C.Cl[Pd]Cl>[ClH:1].[F:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 27343342,4-Difluorophenylboronic acidHCID 2736842Methyl 2-chloropyridine-4-carboxylate

Produkt 1

HCID 66731571Methyl 2-(2,4-difluorophenyl)isonicotinate hydrochlorideAusbeute 80,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24290Palladium ChlorideKatalysatorHCID 887MethanolLösungsmittelHCID 15413tert-Butyl methyl etherLösungsmittel2×

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

Methyl 2-chloroisonicotinate (3 g, 17.48 mmol), 2,4-difluorophenylboronic acid (4.14 g, 26.23 mmol), potassium carbonate (1.812 g, 13.11 mmol) and PdCl2 (dppf) (0.380 g, 0.52 mmol) were mixed in methanol (30 mL) in two separate 20 mL microwave vials. The vials were capped and heated at 100° C. for 10 min in a single node microwave reactor. Water and DCM were added and the phases were separated. The water phase (pH 9) was extracted with DCM and the combined organic phase washed with brine, passed through a phase separator and evaporated to yield a brown solid. The solid was dissolved in MTBE and stirred for 15 minutes, then filtered. The orange MTBE layer was treated with hydrogen chloride (4 M in dioxane, 4.37 mL, 17.48 mmol) and stirred for 1 h at room temperature. The formed solid was collected by filtration. Methyl 2-(2,4-difluorophenyl)isonicotinate hydrochloride (4.0 g, 80%) was isolated as a slightly orange solid. MS m/z 250 (M+H)+

Aufarbeitung

  1. customseparate 20 mL microwave vials
  2. customThe vials were capped
  3. additionWater and DCM were added
  4. customthe phases were separated
  5. extractionThe water phase (pH 9) was extracted with DCM
  6. washthe combined organic phase washed with brine
  7. customevaporated
  8. customto yield a brown solid
  9. filtrationfiltered
  10. stirringstirred for 1 h at room temperature
  11. filtrationThe formed solid was collected by filtration

Quellen und Nachweise

ORD-Eintrag
ord-2b1a32d5167649dd8c7de89e2bc44b15
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08415378B2

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