1-Bromo-4-fluorobenzene → (r)-1-(4-Fluorophenyl)-3-methylpiperazine

HRID 1008769Notes

Reaction equation

HRID 1008769 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1.[CH3:9][C@@H:10]1[CH2:15][NH:14][CH2:13][CH2:12][NH:11]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[F:8][C:5]1[CH:6]=[CH:7][C:2]([N:14]2[CH2:13][CH2:12][NH:11][C@H:10]([CH3:9])[CH2:15]2)=[CH:3][CH:4]=1

Participants

7

Reactant 3

HCID 99931-Bromo-4-fluorobenzeneHCID 73304342-Methylpiperazine, (R)-HCID 23676156Sodium t-butoxide

Product 1

HCID 57435413(r)-1-(4-Fluorophenyl)-3-methylpiperazineYield 46%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolvent

Procedure

To a mixture of 1-bromo-4-fluorobenzene (5.0 g, 0.0285 mol), (R)-2-methylpiperazine (3.15 g, 0.0313 mol) and sodium-tert-butoxide (4 g, 0.042 mol) in dry toluene (100 mL) under nitrogen was added Pd(OAc)2 (0.25 g, 0.0011 mol) followed by BINAP (0.75 g, 0.0012 mol). The reaction mixture was then refluxed for 18 h and cooled down to rt. The reaction mixture was washed with water, dried over magnesium sulfate, filtrated and concentrated. Purification of the crude by chromatography on silica (chloroform:MeOH, 8:2) gave the title compound as a liquid (2.5 g, 46% yield). TLC: Rf=0.25 (Chloroform/MeOH: 9/1).

Workup

  1. temperatureThe reaction mixture was then refluxed for 18 h
  2. washThe reaction mixture was washed with water
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltrated
  5. concentrationconcentrated
  6. customPurification of the crude by chromatography on silica (chloroform:MeOH, 8:2)

Sources & evidence

ORD record
ord-7066f1392bca4860a8be7a3fd18a8ce5
Source dataset
uspto-grants-2011_07
Patent number
US07973039B2

Reaction notes

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