4-Bromo-4'-fluoro-1,1'-biphenyl → HCID 58487952, compound

HRID 888191Notes

Reaction equation

HRID 888191 reaction equation
[CH3:1][C@@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][NH:3]1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Br[C:55]1[CH:60]=[CH:59][C:58]([C:61]2[CH:66]=[CH:65][C:64]([F:67])=[CH:63][CH:62]=2)=[CH:57][CH:56]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:67][C:64]1[CH:63]=[CH:62][C:61]([C:58]2[CH:59]=[CH:60][C:55]([N:6]3[CH2:5][CH2:4][NH:3][C@H:2]([CH3:1])[CH2:7]3)=[CH:56][CH:57]=2)=[CH:66][CH:65]=1

Participants

7

Reactant 4

HCID 968824-Bromo-4'-fluoro-1,1'-biphenylHCID 634876Binap, (A+-)-HCID 73304342-Methylpiperazine, (R)-HCID 23676156Sodium t-butoxide

Product 1

HCID 58487952HCID 58487952, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (R)-2-methylpiperazine (2.2 g, 22.1 mmol, 1.0 eq.), tris(dibenzylidene acetone)dipalladium(0) (607 mg, 0.66 mmol, 0.03 eq.) and (+/−)-BINAP (137 mg, 0.22 mmol; 0.01 eq.) in toluene was degassed 15 min under N2. 4-bromo-4′-fluorobiphenyl (4.99 g, 19.9 mmol, 0.90 eq.) was added followed by sodium tert-butoxide (2.97 g, 30.9 mmol, 1.4 eq.). The resulting mixture was heated to 90° C. for 14 h. The reaction was cooled to room temperature, filtered on a bed of cellite and washed with Et2O. The combined organic layers were then washed with H2O (3×), dried over MgSO4, filtered and evaporated to give a dark brown oil. This residue was purified by chromatography on silicagel (DCM/MeOH 20/80) to give the title product as off white solid (3.0 g, 50%) M+(ESI): 271.3. HPLC (Condition A), Rt: 2.8 min (HPLC purity: 99.8%).

Workup

  1. customwas degassed 15 min under N2
  2. temperatureThe reaction was cooled to room temperature
  3. filtrationfiltered on a bed of cellite
  4. washwashed with Et2O
  5. washThe combined organic layers were then washed with H2O (3×)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customto give a dark brown oil
  10. customThis residue was purified by chromatography on silicagel (DCM/MeOH 20/80)

Sources & evidence

ORD record
ord-e30c30f8202a4c03823de19e0edd85f3
Source dataset
uspto-grants-2012_08
Patent number
US08247437B2

Reaction notes

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