Piperazine → HCID 68594568, compound

HRID 220447Notes

Reaction equation

HRID 220447 reaction equation
Br[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>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:14][C:11]1[CH:12]=[CH:13][C:8]([C:7]2[C:2]([N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)=[N:3][CH:4]=[CH:5][CH:6]=2)=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 4837PiperazineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 86641648HCID 86641648, compound

Product 1

HCID 68594568HCID 68594568, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Dissolve 2-bromo-3-(4-fluorophenyl)-pyridine (4.4 g, 17.5 mmol) in toluene (185 mL) and add piperazine (4.5 g, 52.4 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.8 g, 0.873 mmol), sodium-t-butoxide (2.35 g, 24.4 mmol) and racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (1.63 g, 2.62 mmol). Reflux the mixture for 18 hr.s, then cool to room temperature and filter through Celite®. Dilute the mixture with ethyl acetate and wash with saturated aqueous sodium bicarbonate, saturated aqueous sodium chloride, dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 15:85 2 M ammonia in methanol:DCM) to give the title preparation as a yellow solid (3.9 g, 87%). MS (APCI): m/z=258 [M+H]+.

Workup

  1. temperatureReflux the mixture for 18 hr
  2. filtrationfilter through Celite®
  3. additionDilute the mixture with ethyl acetate
  4. washwash with saturated aqueous sodium bicarbonate, saturated aqueous sodium chloride
  5. dry with materialdry (sodium sulfate)
  6. filtrationfilter
  7. concentrationconcentrate
  8. custompurify
  9. wash(silica gel chromatography, eluting with 15:85 2 M ammonia in methanol:DCM)
  10. customto give the title

Sources & evidence

ORD record
ord-892633d4fd184a0685fad1c90e1d154f
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

Loading…