1-Methylpiperazine → 1-(2-Chloropyridin-4-YL)-4-methylpiperazine

HRID 885950

Reaction equation

HRID 885950 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][N:3]=1.[CH3:9][N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.[Cl-].[Cl-].[Fe+2].[Pd+2]>[Cl:1][C:2]1[CH:7]=[C:6]([N:13]2[CH2:14][CH2:15][N:10]([CH3:9])[CH2:11][CH2:12]2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 531671-MethylpiperazineHCID 15165112-Chloro-4-iodopyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 722188991-(2-Chloropyridin-4-YL)-4-methylpiperazineYield 77%

Reagents, catalysts & solvents 2

HCID 53384307Dichloro[1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
115 °C

Procedure

To a mixture of 2-chloro-4-iodopyridine (300 mg, 1.24 mmol) in toluene (4 mL) was added 1-methylpiperazine (0.14 mL, 1.24 mmol), sodium tert-butoxide (239 mg, 2.44 mmol), [1,1′-bis(di-tert-butylphosphino)ferrocene]palladium(II) dichloride (30 mg, 10% wt) and the suspension was heated to 115° C. under microwave irradiation for 30 minutes. The resulting mixture was concentrated in vacuo and partitioned between DCM (50 mL) and water (50 mL). The organic phase was washed with brine (50 mL), dried (MgSO4), and evaporated in vacuo to give the title compound (200 mg, 77%) as a brown oil. LCMS (ES+) 212.0 (M+H)+, RT 1.78 minutes (70% purity) (Method 2).

Workup

  1. concentrationThe resulting mixture was concentrated in vacuo
  2. custompartitioned between DCM (50 mL) and water (50 mL)
  3. washThe organic phase was washed with brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-36642310d6664144b76b5f68ff44f51e
Source dataset
uspto-grants-2012_08
Patent number
US08242116B2

Linked notes

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