Piperazine → 1-(4-((tetrahydro-2H-pyran-2-yloxy)methyl)pyridin-2-yl)piperazine

HRID 517558Notes

Reaction equation

HRID 517558 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH2:8][O:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][O:11]2)[CH:5]=[CH:4][N:3]=1.[NH:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1>CCN(C(C)C)C(C)C.O>[O:11]1[CH2:12][CH2:13][CH2:14][CH2:15][CH:10]1[O:9][CH2:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([N:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH:7]=1

Participants

5

Reactant 2

HCID 4837PiperazineHCID 860901042-chloro-4-((tetrahydro-2H-pyran-2-yloxy)methyl)pyridine

Product 1

HCID 867114981-(4-((tetrahydro-2H-pyran-2-yloxy)methyl)pyridin-2-yl)piperazineYield 80.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 81531DiisopropylethylamineSolvent

Procedure

A solution of 2-chloro-4-((tetrahydro-2H-pyran-2-yloxy)methyl)pyridine (8.7 g, 38.2 mmol) and piperazine (16.4 g, 191 mmol) in DIEA (30 mL) was heated at 150° C. for 48 h. The reaction mixture was diluted with H2O (1000 mL), and the solution was extracted with DCM/MeOH (10/1, 3×400 mL). The combined organic layers were washed with H2O (100 mL), and brine (100 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (DCM:MeOH=15:1) to afford 1-(4-((tetrahydro-2H-pyran-2-yloxy)methyl)pyridin-2-yl) piperazine as yellow oil (8.5 g, 80%). MS (ES+) C15H23N3O2 requires: 277, found: 278[M+H]+.

Workup

  1. extractionthe solution was extracted with DCM/MeOH (10/1, 3×400 mL)
  2. washThe combined organic layers were washed with H2O (100 mL), and brine (100 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography (DCM:MeOH=15:1)

Sources & evidence

ORD record
ord-37099c0602e54ed6b01bdb8b973bc3a2
Source dataset
uspto-grants-2015_08
Patent number
US09115120B2

Reaction notes

Loading…