4-Bromo-4'-fluoro-1,1'-biphenyl → 3-[2-(4'-Fluorobiphenyl-4-yl)ethynyl]quinuclidin-3-ol

HRID 964599Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 964599
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[C:15]([C:17]1([OH:25])[CH:22]2[CH2:23][CH2:24][N:19]([CH2:20][CH2:21]2)[CH2:18]1)#[CH:16]>C(N(CC)CC)C.O.[OH-].[Na+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[F:14][C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:6]=[CH:7][C:2]([C:16]#[C:15][C:17]3([OH:25])[CH:22]4[CH2:23][CH2:24][N:19]([CH2:20][CH2:21]4)[CH2:18]3)=[CH:3][CH:4]=2)=[CH:9][CH:10]=1

Komponenten

8

Edukt 2

HCID 968824-Bromo-4'-fluoro-1,1'-biphenylHCID 36135173-Ethynyl-1-azabicyclo[2.2.2]octan-3-ol

Produkt 1

HCID 190775533-[2-(4'-Fluorobiphenyl-4-yl)ethynyl]quinuclidin-3-olAusbeute 16,5 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 6102075Dichlorobis(triphenylphosphine)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 8471TriethylamineLösungsmittelHCID 14798Sodium HydroxideLösungsmittel

Versuchsvorschrift

A mixture of 4-bromo-4'-fluorobiphenyl (1.0 g), 3-ethynyl-3-hydroxyquinuclidine (600 mg), bis(triphenylphosphine)-palladium (II) chloride (120 mg) and copper (I) iodide (60 mg) in dry triethylamine (15 ml) was stirred at reflux under an atmosphere of argon for 5 hours. The reaction mixture was cooled, diluted with water (60 ml), 2H aqueous sodium hydroxide solution added and extracted with dichloromethane. The mixed layers were filtered through diatomaceous earth and washed with dichloromethane. The organic layer in the filtrate was separated, dried (MgSO4) and evaporated to a residue which was further purified by flash column chromatography on alumina (ICN Alumina N 32-63) using a mixture of 10% ethanol in ethyl acetate as eluent to give a residue which was crystallised from a mixture of 10% ethanol in ethyl acetate to give 3-[2-(4'-fluorobiphenyl-4-yl)ethynyl]quinuclidin-3-ol (210 mg) as a solid, m.p. 232-233° C.; microanalysis, found: C, 78.0; H, 6.4; N, 4.5%; C21H20FN0.O.1H2O requires C,78.07; H,6.26; N, 4.34%; NMR (DMSO-d6): 1.2-1.4(1H, m), 1.5-1.7(1H, m), 1.8-2.01(3H, m), 2.6-2.8(4H, t), 2.8-3.15(2H, d of d), 5.6(1H, s), 7.22-7.4(2H, m), 7.45-7.55(2H, d) and 7.61-7.81(4H, m); m/z 322 (M+H).

Aufarbeitung

  1. temperatureat reflux under an atmosphere of argon for 5 hours
  2. temperatureThe reaction mixture was cooled
  3. additionadded
  4. extractionextracted with dichloromethane
  5. filtrationThe mixed layers were filtered through diatomaceous earth
  6. washwashed with dichloromethane
  7. customThe organic layer in the filtrate was separated
  8. dry with materialdried (MgSO4)
  9. customevaporated to a residue which
  10. customwas further purified by flash column chromatography on alumina (ICN Alumina N 32-63)
  11. additiona mixture of 10% ethanol in ethyl acetate as eluent
  12. customto give a residue which
  13. customwas crystallised from a mixture of 10% ethanol in ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-7eb6da5f79a44e35bdffd5612402e27e
Quelldatensatz
uspto-grants-1998_06
Patentnummer
US05770608

Notizen zur Reaktion

Wird geladen…