Hydrochloric Acid → 5-(3-Chloro-4-fluorophenyl)-6-(2,2,2-trifluoroethoxy)nicotinic acid

HRID 1025983Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1025983
Br[C:2]1[CH:3]=[C:4]([C:14]([OH:16])=[O:15])[CH:5]=[N:6][C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].[Cl:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[CH:22][C:23]=1[F:24].C([O-])([O-])=O.[Na+].[Na+].Cl>C1(C)C=CC=CC=1.CN(C=O)C>[Cl:17][C:18]1[CH:19]=[C:20]([C:2]2[C:7]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])=[N:6][CH:5]=[C:4]([CH:3]=2)[C:14]([OH:16])=[O:15])[CH:21]=[CH:22][C:23]=1[F:24]

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 581925925-Bromo-6-(2,2,2-trifluoroethoxy)-3-pyridinecarboxylic acid

Produkt 1

HCID 666788425-(3-Chloro-4-fluorophenyl)-6-(2,2,2-trifluoroethoxy)nicotinic acidAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

5-Bromo-6-(2,2,2-trifluoroethoxy)-3-pyridinecarboxylic acid (CAN 1211586-75-2; 1.5 g; 5.0 mmol) was dissolved in toluene (35 mL) an DMF (2 mL). To this solution was added 1,1′-bis(diphenylphosphino)-ferrocene-palladium(II)dichloride dichloromethane complex (204 mg, 250 μmol), followed by 3-chloro-4-fluorophenylboronic acid (CAN 144432-85-9; 959 mg, 5.5 mmol) and 2M—Na2CO3 (20.0 ml, 40.0 mmol). The reaction mixture was heated to 90° C. and stirred for 4 h, cooled and poured into 100 mL ice water, acidified with 45 mL 2N—HCl and extracted ethyl acetate. The organic layers were combined, dried with Na2SO4 and concentrated in vacuo. The crude material was crystallized from heptane:ethyl acetate (5:1) to yield 1.1 g (63%) of the title compound as light grey solid; LC-MS (UV peak area/ESI): 97%, 348.0066 (M−H)−.

Aufarbeitung

  1. additionTo this solution was added 1,1′-bis(diphenylphosphino)-ferrocene-palladium(II)dichloride dichloromethane complex (204 mg, 250 μmol)
  2. temperaturecooled
  3. extractionextracted ethyl acetate
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was crystallized from heptane:ethyl acetate (5:1)

Quellen und Nachweise

ORD-Eintrag
ord-1594cc1689c24116879ad165bd283b5f
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08729105B2

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