4-Bromo-4'-fluoro-1,1'-biphenyl → HCID 67729347, compound

HRID 2256077Notes

Reaction equation

HRID 2256077 reaction equation
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([C:16]#[C:15][C:17]2([OH:25])[CH:22]3[CH2:23][CH2:24][N:19]([CH2:20][CH2:21]3)[CH2:18]2)[CH:12]=[CH:13][C:8]([C:5]2[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=2)=[CH:9][CH2:10]1

Participants

8

Reactant 2

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

Product 1

HCID 67729347HCID 67729347, compoundYield 16.4%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 8471TriethylamineSolventHCID 14798Sodium HydroxideSolvent

Procedure

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), 2M 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%; C21H20FNO.0.1H2O 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).

Workup

  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

Sources & evidence

ORD record
ord-02b67684257444fe9dec482002720389
Source dataset
uspto-grants-1997_08
Patent number
US05654315

Reaction notes

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