Tris(1,1-dimethylethyl)phosphine → Methyl 6-(2,6-difluoro-4-methoxyphenyl)-5-fluoropicolinate

HRID 705183Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 705183
Br[C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][C:3]=1[F:12].[F:13][C:14]1[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[C:16]([F:22])[C:15]=1B(O)O.[F-].[K+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C1COCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:13][C:14]1[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[C:16]([F:22])[C:15]=1[C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][C:3]=1[F:12]

Komponenten

8

Edukt 4

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 522689Potassium FluorideHCID 162174242,6-Difluoro-4-methoxybenzeneboronic acidHCID 46311204Methyl 6-bromo-5-fluoropyridine-2-carboxylate

Produkt 1

HCID 59226460Methyl 6-(2,6-difluoro-4-methoxyphenyl)-5-fluoropicolinateAusbeute 85 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of methyl 6-bromo-5-fluoropicolinate (1.0 equiv.) in THF and water (10:1, 0.1 M) was added 2,6-difluoro-4-methoxyphenylboronic acid (2.5 equiv.) and potassium fluoride (3.3 equiv.). The reaction was degassed with nitrogen, then Pd2(dba)3 (0.25 equiv.) and tri-tert-butylphosphine (0.5 equiv.) were added and the reaction was heated to 80° C. for one hour. LC/MS analysis indicated complete conversion of the starting material to product. The reaction was cooled to room temperature, then concentrated in vacuo and fused to silica gel. The crude product was purified by ISCO flash chromatography eluting with ethyl acetate and hexanes (0% to 30% ethyl acetate) to provide methyl 6-(2,6-difluoro-4-methoxyphenyl)-5-fluoropicolinate as a white solid in 85% yield. LC/MS=298.0 (M+H), Rt=0.89 min.

Aufarbeitung

  1. customThe reaction was degassed with nitrogen
  2. temperatureThe reaction was cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by ISCO flash chromatography
  5. washeluting with ethyl acetate and hexanes (0% to 30% ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-f12289236517459faab528343748fba3
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09173883B2

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