Rolipram → 3-[4-(3-Cyclopentyloxy-4-methoxy-phenyl)-2-oxo-pyrrolidin-1-yl]benzonitrile

HRID 1727136

Reaction equation

HRID 1727136 reaction equation
[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:15]3[CH2:19][NH:18][C:17](=[O:20])[CH2:16]3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[C:25]#[N:26].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[C@@H]1(N)CCCC[C@H]1N>CCOC(C)=O.[Cu]I.O1CCOCC1.CN(C=O)C>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:15]3[CH2:19][N:18]([C:22]4[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=4)[C:25]#[N:26])[C:17](=[O:20])[CH2:16]3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

9

Reactant 4

HCID 5092RolipramHCID 233813-BromobenzonitrileHCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, Tribasic

Product 1

HCID 104746693-[4-(3-Cyclopentyloxy-4-methoxy-phenyl)-2-oxo-pyrrolidin-1-yl]benzonitrileYield 96.2%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 4-(3-cyclopentyloxy-4-methoxyphenyl)-pyrrolidin-2-one (1.5 g, 5 mmol), 3-bromobenzonitrile (1.36 g, 7.5 mmol), potassium phosphate (1.9 g, 9.8 mmol), and 1,2-trans-cyclohexanediamine (60 μL) was created in a dry round bottom flask under nitrogen containing DMF (9 mL) and dioxane (9 mL). The mixture was stirred and CuI (100 mg) was added. The resulting reaction mixture was heated to 110° C. with stirring under N2 for 20 h, and then cooled to r.t. The mixture was diluted with EtOAc and then filtered. The filtrate was washed with saturated aqueous solutions of NH4Cl and brine, dried over MgSO4, and concentrated under reduced pressure. Chromatography on silica gel (EtOAc:hexane=1:3 to 1:1) gave 1.81 g of 3-[4-(3-cyclopentyloxy-4-methoxy-phenyl)-2-oxo-pyrrolidin-1-yl]benzonitrile. Yield: 90%.

Workup

  1. customwas created in a dry round bottom flask under nitrogen
  2. customThe resulting reaction mixture
  3. stirringwith stirring under N2 for 20 h
  4. temperaturecooled to r.t
  5. filtrationfiltered
  6. washThe filtrate was washed with saturated aqueous solutions of NH4Cl and brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d126f3eed8c14591a419ca2157fcb205
Source dataset
uspto-grants-2009_02
Patent number
US07495016B2

Linked notes

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