Sodium Hydroxide → 6-(2,6-Difluorophenyl)pyridine-3-carboxylic acid

HRID 2053692Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2053692
C([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]([C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=2[F:19])=[CH:10][CH:11]=1)=[O:5])C.[OH-].[Na+]>CO>[F:19][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]([F:18])[C:12]=1[C:9]1[N:8]=[CH:7][C:6]([C:4]([OH:5])=[O:3])=[CH:11][CH:10]=1

Komponenten

4

Edukt 2

HCID 14798Sodium HydroxideHCID 69129633Ethyl 6-(2,6-difluorophenyl)-3-pyridinecarboxylate

Produkt 1

HCID 532230666-(2,6-Difluorophenyl)pyridine-3-carboxylic acidAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

Combine the mixture as obtained above (0.225 g, 1.04 mmol) with hexamethylditin (0.375 g, 1.15 mmol), Pd(OAc)2 (21 mg, 0.09 mmol), and triphenylphosphine (25 mg, 0.09 mmol) in toluene (5 mL). Purge with N2 and stir at 80° C. for 18 hours. Cool reaction to room temperature. Add a solution of 1-bromo-2,6-difluorobenzene (250 mg, 1.29 mmol) in toluene (1 mL) followed by Pd(OAc)2 (21 mg, 0.09 mmol) and triphenylphosphine (25 mg, 0.09 mmol). Purge with N2 and stir at 80° C. for an additional 18 hours. Cool reaction to room temperature. Evaporate the solvent and purify by column chromatography (silica, 10% ethyl acetate in hexane) to give 50 mg (20% yield) of 6-(2,6-difluorophenyl)pyridine-3-carboxylic acid ethyl ester. Hydrolyze the ester with 1 N sodium hydroxide solution (0.22 mL, 0.22 mmol) in methanol (3 mL) at room temperature for 3 days. Remove the volatiles under vacuum and combine the residue with 1 N hydrochloric acid solution. Collect the white solid by filtration, wash with water, and dry under vacuum to give 30 mg (63% yield) of the title compound. MS (m/e): 235.9 (MH+).

Aufarbeitung

  1. customat room temperature
  2. customfor 3 days
  3. customRemove the volatiles under vacuum
  4. customCollect the white solid
  5. filtrationby filtration
  6. washwash with water
  7. customdry under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-2d25b01dca904262b4ef9041231e6c1d
Quelldatensatz
uspto-grants-2008_02
Patentnummer
US07326731B2

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