Sodium hydride → 1-(2-Fluoroethyl)-4-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-2-piperazinone

HRID 419444Notes

Reaction equation

HRID 419444 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]([N:14]2[CH2:19][CH2:18][CH:17]([N:20]3[CH2:25][CH2:24][NH:23][C:22](=[O:26])[CH2:21]3)[CH2:16][CH2:15]2)[CH:8]=[CH:9][C:10]=1[N+:11]([O-:13])=[O:12].[F:27][CH2:28][CH2:29]I>CN(C=O)C.C1COCC1>[F:27][CH2:28][CH2:29][N:23]1[CH2:24][CH2:25][N:20]([CH:17]2[CH2:18][CH2:19][N:14]([C:7]3[CH:8]=[CH:9][C:10]([N+:11]([O-:13])=[O:12])=[C:5]([O:4][CH3:3])[CH:6]=3)[CH2:15][CH2:16]2)[CH2:21][C:22]1=[O:26]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 69804Ethane, 1-fluoro-2-iodo-HCID 594529704-{1-[3-(Methyloxy)-4-nitrophenyl]-4-piperidinyl}-2-piperazinone

Product 1

HCID 594526081-(2-Fluoroethyl)-4-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-2-piperazinoneYield 76%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

NaH (60% dispersion in mineral oil, 0.174 g, 4.35 mmol) was washed two times with hexanes. 10 mL of DMF and 5 mL of THF was added via syringe. 4-{1-[3-(Methyloxy)-4-nitrophenyl]-4-piperidinyl}-2-piperazinone (0.970 g, 2.90 mmol) in 20 mL of DMF and 10 mL of THF was added slowly via syringe. The reaction was stirred for 45 min, and 1-fluoro-2-iodoethane (0.28 mL, 3.4 mmol) was added via syringe. The reaction was stirred overnight and quenched by the addition of H2O. The mixture was poured into EtOAc and H2O, and the layers were separated. The organic layer was washed with brine, and the combined aqueous layers were extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford 0.834 g (76%) of the title compound of step B. 1H NMR (400 MHz, DMSO-d6) δ 7.83 (d, J=9.0 Hz, 1H), 6.55 (dd, J=9.4, 2.5 Hz, 1H), 6.46 (d, J=2.4 Hz, 1H), 4.55 (t, J=4.9 Hz, 1H), 4.44 (t, J=4.9 Hz, 1H), 4.07-3.94 (m, 2H), 3.86 (s, 3H), 3.58 (t, J=4.9 Hz, 1H), 3.51 (t, J=5.1 Hz, 1H), 3.34-3.22 (m, 2H), 3.11 (s, 2H), 2.99-2.86 (m, 2H), 2.68 (t, J=5.2 Hz, 2H), 2.57-2.46 (m, 1H), 1.89-1.76 (m, 2H), 1.49-1.32 (m, 2H).

Workup

  1. stirringThe reaction was stirred overnight
  2. customquenched by the addition of H2O
  3. additionThe mixture was poured into EtOAc and H2O
  4. customthe layers were separated
  5. washThe organic layer was washed with brine
  6. extractionthe combined aqueous layers were extracted with EtOAc
  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-fa5ec27ed65c40e5b9e2ddb0e592c0b0
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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