Sodium hydride → 4-[(2,4-dichlorophenyl)amino]-3-{2-[4-(1-ethoxyethoxy)phenyl]-1-methyl-2-oxoethyl}-1-piperidin-1-yl-5,6-dihydropyridin-2(1H)-one

HRID 2102873Notes

Reaction equation

HRID 2102873 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[CH2:15][CH2:14][N:13]([N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[C:12](=[O:22])[CH:11]=1.[H-].[Na+].Br[CH:26]([CH3:41])[C:27]([C:29]1[CH:34]=[CH:33][C:32]([O:35][CH:36]([O:38][CH2:39][CH3:40])[CH3:37])=[CH:31][CH:30]=1)=[O:28]>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[CH2:15][CH2:14][N:13]([N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[C:12](=[O:22])[C:11]=1[CH:26]([CH3:41])[C:27]([C:29]1[CH:34]=[CH:33][C:32]([O:35][CH:36]([O:38][CH2:39][CH3:40])[CH3:37])=[CH:31][CH:30]=1)=[O:28]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 442497124-[(2,4-dichlorophenyl)amino]-1-piperidin-1-yl-5,6-dihydropyridin-2(1H)-oneHCID 442497132-Bromo-1-[4-(1-ethoxyethoxy)phenyl]propan-1-one

Product 1

HCID 250296504-[(2,4-dichlorophenyl)amino]-3-{2-[4-(1-ethoxyethoxy)phenyl]-1-methyl-2-oxoethyl}-1-piperidin-1-yl-5,6-dihydropyridin-2(1H)-oneYield 138.9%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

4-[(2,4-dichlorophenyl)amino]-1-piperidin-1-yl-5,6-dihydropyridin-2(1H)-one (450 mg, 1.323 mmol) suspended in THF (7 ml) was added during 15 min to NaH (67 mg, 2.645 mmol) suspended in THF (5 ml) at 5° C. under nitrogen. After the resulting mixture had been stirred at 0° C. for 1 h tetrabutylammonium iodide (49 mg, 0.132 mmol) was added followed by dropwise addition of 2-bromo-1-[4-(1-ethoxyethoxy)phenyl]propan-1-one (597 mg, 1.984 mmol) dissolved in THF (5 ml) during 15 min. After the addition the cooling bath was removed and the reaction was continued at rt overnight. Water was added and the solvent was removed by evaporation. The residue was partitioned between DCM and water. The organic phase was dried (MgSO4), filtered and evaporated to yield an orange oil (1.030 g, 90%).

Workup

  1. additionwas added
  2. additionAfter the addition the cooling bath
  3. customwas removed
  4. additionWater was added
  5. customthe solvent was removed by evaporation
  6. customThe residue was partitioned between DCM and water
  7. dry with materialThe organic phase was dried (MgSO4)
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-f19bad9e5e5e414f8ac117ac4af3749f
Source dataset
uspto-grants-2009_08
Patent number
US07576095B2

Reaction notes

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