Potassium hydride → 4-Benzyloxy [4-(4-pyridyl)piperazin-2-one-1-yl]benzene

HRID 2252

Reaction equation

HRID 2252 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][NH:10][C:9](=[O:13])[CH2:8]2)=[CH:3][CH:2]=1.[H-].[K+].[CH2:16]([O:23][C:24]1[CH:29]=[CH:28][C:27](Br)=[CH:26][CH:25]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CN(C)C=O.O.[Cl-].[Na+].O.[Cu]I>[NH3:1].[CH2:16]([O:23][C:24]1[CH:29]=[CH:28][C:27]([N:10]2[CH2:11][CH2:12][N:7]([C:4]3[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=3)[CH2:8][C:9]2=[O:13])=[CH:26][CH:25]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

9

Reactant 3

HCID 82127Potassium hydrideHCID 1388351-Bromo-4-phenylmethoxybenzeneHCID 189183564-(Pyridin-4-YL)piperazin-2-one

Product 2

HCID 222AmmoniaHCID 542272954-Benzyloxy [4-(4-pyridyl)piperazin-2-one-1-yl]benzeneYield 123.3%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a stirred suspension of 4-(4-pyridyl) piperazin-2-one (880 mg) in dimethyl formamide (20 ml) was added potassium hydride (1.0 ml of a 20% dispersion) and the mixture stirred for 0.5 hr, after which time was added copper (I) iodide (1.0 g). After 0.25 hr there was added 4-benzyloxybromobenzene (1.2 g) and the mixture stirred at 140° C. in an argon atmosphere for 2 hr. The reaction mixture was diluted with water and brine and extracted with dichloromethane (3×40 ml); the combined extracts were washed with water and brine, dried (PS paper) and evaporated to give crude product as a pasty solid (2.0 g). This was purified by flash chromatography on silica, eluting with dichloromethane/methanol/conc. ammonia (97:2.5:0.5 v/v) to give 4-benzyloxy [4-(4-pyridyl)piperazin-2-one-1-yl]benzene as a colourless solid (1.1 g) NMR δ (d6DMSO): 3.7-3.9 (4H,m); 4.1 (2H,s); 5.1 (2H,s); 6.85 (2H,d); 7.05 (2H,d); 7.25 (2H,d); 7.3-7.6 (5H,m); 8.2 (2H,d); m/e 360 (M+H)+.

Workup

  1. stirringthe mixture stirred at 140° C. in an argon atmosphere for 2 hr
  2. extractionextracted with dichloromethane (3×40 ml)
  3. washthe combined extracts were washed with water and brine
  4. customdried (PS paper)
  5. customevaporated
  6. customto give crude product as a pasty solid (2.0 g)
  7. customThis was purified by flash chromatography on silica
  8. washeluting with dichloromethane/methanol/conc

Sources & evidence

ORD record
ord-35c0a06e7c3d4c9f82f5835490d4df81
Source dataset
uspto-grants-1998_03
Patent number
US05728701

Linked notes

Loading…