Sodium hydride → 2-Chloro-5-((3-(4-(4-methoxybenzoyl)piperidin-1-yl)-2-oxopyrrolidin-1-yl)methyl)benzonitrile

HRID 1752265Notes

Reaction equation

HRID 1752265 reaction equation
[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:19][CH2:18][NH:17][C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:5][CH:4]=1.Br[CH2:24][C:25]1[CH:26]=[CH:27][C:28]([Cl:33])=[C:29]([CH:32]=1)[C:30]#[N:31].[H-].[Na+]>C1COCC1.CN(C=O)C>[Cl:33][C:28]1[CH:27]=[CH:26][C:25]([CH2:24][N:17]2[CH2:18][CH2:19][CH:15]([N:12]3[CH2:13][CH2:14][CH:9]([C:7](=[O:8])[C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:22][CH:21]=4)[CH2:10][CH2:11]3)[C:16]2=[O:20])=[CH:32][C:29]=1[C:30]#[N:31]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 140330355-(Bromomethyl)-2-chlorobenzonitrileHCID 712122103-(4-(4-Methoxybenzoyl)piperidin-1-yl)pyrrolidin-2-one

Product 1

HCID 712122312-Chloro-5-((3-(4-(4-methoxybenzoyl)piperidin-1-yl)-2-oxopyrrolidin-1-yl)methyl)benzonitrile

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 3-(4-(4-methoxybenzoyl)piperidin-1-yl)pyrrolidin-2-one (70 mg, 0.232 mmol) and 5-(bromomethyl)-2-chlorobenzonitrile (80 mg, 0.347 mmol) in THF (1 mL) and DMF (0.1 mL) was added NaH (46.3 mg, 1.16 mmol, 60%). The reaction was concentrated in vacuo then taken up in dichlormethane and MeOH and filtered through a short plug of silica gel. The pooled fractions containing the title material were pooled, concentrated and neutralized with NaHCO3. MeOH was added and the solution was cooled in a freezer. The title compound was obtained by collecting the white solid via filtration (45 mg). HRMS calculated for C25H26ClN3O3 451.1671. found (ESI, [M+H]+) 452.1744.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. filtrationMeOH and filtered through a short plug of silica gel
  3. additionThe pooled fractions containing the title material
  4. concentrationconcentrated
  5. additionMeOH was added
  6. temperaturethe solution was cooled in a freezer

Sources & evidence

ORD record
ord-a906a9f9e7564c82952bdf11cad3ff7d
Source dataset
uspto-grants-2015_10
Patent number
US09163003B2

Reaction notes

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