Acetic Acid → 4-{1-[3-(Methyloxy)-4-nitrophenyl]-4-piperidinyl}-2-piperazinone

HRID 419443Notes

Reaction equation

HRID 419443 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10].[NH:19]1[CH2:24][CH2:23][NH:22][CH2:21][C:20]1=[O:25].CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1(C)C=CC=CC=1.C(#N)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:17][CH2:16][CH:15]([N:22]3[CH2:23][CH2:24][NH:19][C:20](=[O:25])[CH2:21]3)[CH2:14][CH2:13]2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 231360Piperazin-2-oneHCID 5049666Sodium triacetoxyborohydrideHCID 259188571-(3-Methoxy-4-nitrophenyl)piperidin-4-one

Product 1

HCID 594529704-{1-[3-(Methyloxy)-4-nitrophenyl]-4-piperidinyl}-2-piperazinoneYield 73%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Procedure

1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinone (Example 57, step B) (1.00 g, 4.00 mmol) and 2-piperazinone (0.801 g, 8.00 mmol) were dissolved in 50 mL of toluene and 25 mL of acetonitrile with stirring. TEA (1.40 mL, 9.97 mmol) and HOAc (0.34 mL, 5.9 mmol) were added via syringe. Sodium triacetoxyborohydride (2.12 g, 10.0 mmol) was added in four equal portions over 1 h. The reaction was allowed to stir overnight and quenched by the addition of approximately 50 mL of 1N NaOH solution and 50 mL of MeOH. The mixture was stirred for 10 min and poured into H2O and EtOAc. The layers were separated, and the organic layer was washed with brine. The combined aqueous layers were extracted with DCM. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford 0.970 g (73%) of the title compound of step A. 1H NMR (400 MHz, DMSO-d6) δ 7.83 (d, J=9.5 Hz, 1H), 7.68 (br. s., 1H), 6.55 (dd, J=9.5, 2.4 Hz, 1H), 6.46 (d, J=2.56 Hz, 1H), 4.07-3.94 (m, 2H), 3.86 (s, 3H), 3.07 (br. s., 2H), 3.00 (s, 2H), 2.97-2.86 (m, 2H), 2.66-2.37 (m, 3H), 1.87-1.75 (m, 2H), 1.48-1.32 (m, 2H).

Workup

  1. customquenched by the addition of approximately 50 mL of 1N NaOH solution and 50 mL of MeOH
  2. stirringThe mixture was stirred for 10 min
  3. additionpoured into H2O and EtOAc
  4. customThe layers were separated
  5. washthe organic layer was washed with brine
  6. extractionThe combined aqueous layers were extracted with DCM
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-4b8515259e434d018f1966a8d6538228
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

Loading…