1,10-Phenanthroline → 1-[5-(Benzyloxy)pyridin-2-yl]piperazine

HRID 1723810Notes

Reaction equation

HRID 1723810 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1.N1[C:27]2[C:18](=[CH:19][CH:20]=[C:21]3[C:26]=2N=CC=C3)[CH:17]=CC=1.C(=O)([O-])[O-:29].[Cs+].[Cs+]>C(O)C1C=CC=CC=1.C(Cl)Cl.[Cu]I>[CH2:17]([O:29][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1)[C:18]1[CH:27]=[CH:26][CH:21]=[CH:20][CH:19]=1

Participants

7

Reactant 3

HCID 13181,10-PhenanthrolineHCID 10796Cesium carbonateHCID 164142271-(5-Bromopyridin-2-yl)piperazine

Product 1

HCID 222215041-[5-(Benzyloxy)pyridin-2-yl]piperazine

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 244Benzyl AlcoholSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A vigorously stirred suspension of 1-(5-bromopyridin-2-yl)piperazine (CAS number 73406-97-0, 116 g, 479 mmol), 1,10-phenanthroline (17.3 g, 96 mmol), Cesium carbonate (312 g, 960 mmol) and Copper (I) iodide (91 g, 480 mmol) in benzyl alcohol (960 mL) was stirred at 120° C. under an inert atmosphere for 24 hours, adding further aliquots of copper (I) iodide (5×91 g) every hour. Cooled to 40° C. and diluted with DCM (1L), stirring at room temperature for 30 minutes. Filtered through celite, washing well with DCM (500 mL). The fractions were washed with NaOH (2M, 300 mL), combined and extracted with HCl (2M, 5×1L). The combined acidic extracts were washed with DCM (500 mL), cooled to 0° C. and extracted into DCM (1L), basifying slowly with NaOH (˜46 wt %) to pH10. The aqueous layer was further extracted with DCM (2×500 mL) and the volatiles removed in vacuo, to give 1-[5-(benzyloxy)pyridin-2-yl]piperazine as a black liquor (104 g, 278 mmol @ 72 wt %, 58%).

Workup

  1. temperatureCooled to 40° C.
  2. stirringstirring at room temperature for 30 minutes
  3. filtrationFiltered through celite
  4. washwashing well with DCM (500 mL)
  5. washThe fractions were washed with NaOH (2M, 300 mL)
  6. extractionextracted with HCl (2M, 5×1L)
  7. washThe combined acidic extracts were washed with DCM (500 mL)
  8. temperaturecooled to 0° C.
  9. extractionextracted into DCM (1L)
  10. extractionThe aqueous layer was further extracted with DCM (2×500 mL)
  11. customthe volatiles removed in vacuo

Sources & evidence

ORD record
ord-41f8b5fb1c31496a9f2284f859b4286d
Source dataset
uspto-grants-2009_02
Patent number
US07485644B2

Reaction notes

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