Sodium hydride → HCID 42633997, compound

HRID 2262484Notes

Reaction equation

HRID 2262484 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH:3]1[CH2:9][CH2:10][OH:11].[H-].[Na+].[C:14]1([N:20]2[CH2:25][CH2:24][N:23]([C:26](OC3C=CC([N+]([O-])=O)=CC=3)=[O:27])[CH2:22][CH2:21]2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1COCC1>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH:3]1[CH2:9][CH2:10][O:11][C:26]([N:23]1[CH2:24][CH2:25][N:20]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:21][CH2:22]1)=[O:27]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 587843272-(1,4-Dimethylpiperazin-2-yl)ethanolHCID 595944814-Nitrophenyl 4-phenylpiperazine-1-carboxylate2×

Product 1

HCID 42633997HCID 42633997, compoundYield 15.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

2-(1,4-Dimethylpiperazin-2-yl)ethanol (703 mg, 4.44 mmol) was dissolved in anhydrous THF (20 mL) and the stirred solution cooled to 0° C. before NaH (60% dispersion in mineral oil; 550 mg, 13.8 mmol) was added. The suspension was left to stir for 10 minutes. 4-Nitrophenyl 4-phenylpiperazine-1-carboxylate (Intermediate 2; 1.89 g, 5.77 mmol) was added to the reaction mixture, which was left to stir at room temperature for 3 hours. After this time the reaction was terminated by cooling the mixture to 0° C. and cautiously quenching with saturated aqueous NaHCO3 solution (50 mL). The THF was removed in vacuo and transferred to a separating funnel where the organic product was extracted with EtOAc (3×75 mL). The combined organic extracts were collected together and washed with saturated aqueous NaHCO3 solution (3×75 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo to give a crude yellow slurry. The crude residue was purified by reverse phase column chromatography (LiChroprep RP-18, 40-63 μm, 460×26 mm (100 g), 30 mL/min, gradient 0% to 15% (over 70 min) to 100% (over 5 min) MeOH in water with 1% formic acid). De-salting (using K2CO3 in DCM), filtration and concentration in vacuo afforded 4-phenylpiperazine-1-carboxylic acid 2-(1,4-dimethylpiperazin-2-yl)ethyl ester (236 mg, 13%) as a dark yellow oil.

Workup

  1. additionwas added
  2. waitThe suspension was left
  3. waitwas left
  4. stirringto stir at room temperature for 3 hours
  5. customAfter this time the reaction was terminated
  6. customcautiously quenching with saturated aqueous NaHCO3 solution (50 mL)
  7. customThe THF was removed in vacuo
  8. customtransferred to a separating funnel
  9. extractionwhere the organic product was extracted with EtOAc (3×75 mL)
  10. customThe combined organic extracts were collected together
  11. washwashed with saturated aqueous NaHCO3 solution (3×75 mL)
  12. dry with materialThe organic layer was dried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customto give a crude yellow slurry
  16. customThe crude residue was purified by reverse phase column chromatography (LiChroprep RP-18, 40-63 μm, 460×26 mm (100 g), 30 mL/min, gradient 0% to 15% (over 70 min) to 100% (over 5 min) MeOH in water with 1% formic acid)
  17. filtrationDe-salting (using K2CO3 in DCM), filtration and concentration in vacuo

Sources & evidence

ORD record
ord-0fd0795ee0d84faaa0bdefcc8252e2fd
Source dataset
uspto-grants-2010_12
Patent number
US07851471B2

Reaction notes

Loading…