Sodium hydride → HCID 42633817, compound

HRID 2262482Notes

Reaction equation

HRID 2262482 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][N:7]([CH3:10])[CH2:6][C@@H:5]1[CH2:11][OH:12].[C:13]1([N:19]2[CH2:24][CH2:23][N:22]([C:25](OC3C=CC([N+]([O-])=O)=CC=3)=[O:26])[CH2:21][CH2:20]2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>CCCCCCC.C1COCC1>[C:13]1([N:19]2[CH2:20][CH2:21][N:22]([C:25]([O:12][CH2:11][C@H:5]3[CH2:6][N:7]([CH3:10])[CH2:8][CH2:9][N:4]3[CH3:3])=[O:26])[CH2:23][CH2:24]2)[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 28765199(2R)-1,4-Dimethyl-2-piperazinemethanol2×HCID 595944814-Nitrophenyl 4-phenylpiperazine-1-carboxylate2×

Product 1

HCID 42633817HCID 42633817, compoundYield 61.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8900HeptaneSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (1.14 g, 60% dispersion in mineral oil, 28.6 mmol) was suspended in heptane (10 mL) under an argon atmosphere. The heptane was decanted off, and the flask was charged with THF (20 mL) and cooled to 0° C. A solution of 1,4-dimethyl-(R)-2-hydroxymethyl piperazine (Intermediate 4; 1.38 g, 9.5 mmol) in THF (20 mL) was added drop-wise, followed by a solution of the 4-nitrophenyl 4-phenylpiperazine-1-carboxylate (Intermediate 2; 4.06 g, 12.4 mmol) in THF (20 mL). The reaction mixture was allowed to warm to room temperature, stirred for 16 hours, the reaction mixture was cooled to 0° C. then quenched with the drop-wise addition of sat aq NaHCO3 solution and concentrated in vacuo. The residue was dissolved in EtOAc (200 mL), washed with sat aq NaHCO3 solution (4×50 mL), dried (MgSO4) and concentrated in vacuo. The residue was suspended in water:formic acid solution [1:1] (20 mL), filtered and the filtrate was purified by reverse phase column chromatography (gradient eluting with methanol in water, with 1% formic acid in each solvent, 0-15%). The resulting residue was dissolved in DCM (50 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo to give [(2R)-1,4-dimethylpiperazin-2-yl]methyl 4-phenylpiperazine-1-carboxylate (1.93 g, 61%) as a pale yellow solid.

Workup

  1. customThe heptane was decanted off
  2. additionthe flask was charged with THF (20 mL)
  3. temperatureto warm to room temperature
  4. temperaturethe reaction mixture was cooled to 0° C.
  5. customthen quenched with the drop-wise addition of sat aq NaHCO3 solution
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in EtOAc (200 mL)
  8. washwashed with sat aq NaHCO3 solution (4×50 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. filtrationformic acid solution [1:1] (20 mL), filtered
  12. customthe filtrate was purified by reverse phase column chromatography (gradient
  13. washeluting with methanol in water, with 1% formic acid in each solvent, 0-15%)
  14. dissolutionThe resulting residue was dissolved in DCM (50 mL)
  15. stirringstirred with solid K2CO3 for 20 minutes
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-57e5e1d60fea4a51ae1af78ff2635386
Source dataset
uspto-grants-2010_12
Patent number
US07851471B2

Reaction notes

Loading…