Chloroacetonitrile → 2-(3-(4-(4-Methoxybenzoyl)piperidin-1-yl)-2-oxopyrrolidin-1-yl)acetonitrile

HRID 1752249Notes

Reaction equation

HRID 1752249 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.Cl[CH2:24][C:25]#[N:26].[H-].[Na+]>C1COCC1.CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:19][CH2:18][N:17]([CH2:24][C:25]#[N:26])[C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:21][CH:22]=1

Participants

6

Reactant 3

HCID 7856ChloroacetonitrileHCID 24758Sodium hydrideHCID 712122103-(4-(4-Methoxybenzoyl)piperidin-1-yl)pyrrolidin-2-one

Product 1

HCID 893757962-(3-(4-(4-Methoxybenzoyl)piperidin-1-yl)-2-oxopyrrolidin-1-yl)acetonitrile

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 3-[4-(4-methoxy-benzoyl)-piperidin-1-yl]-pyrrolidin-2-one (1.65 mmol, 500 mg) and chloroacetonitrile (1.65 mmol, 0.125 g) in THF (30 mL) and DMF (5 mL) was added sodium hydride (60%, 2.48 mmol, 0.099 g) and heated to 70° C. for 30 min. The reaction was allowed to cool to ambient temperature and dried under vacuum. Flash column chromatography (silica) was performed eluting with ethyl acetate to 20% MeOH/ethyl acetate and provided the title compound as an off-white residue (125 mg, 22.1% yield). Calculated MS=341.4. found MS (ESI) m/e 342.9 (M+H+); HPLC (Novapak 150×3.9 mm C18 column: mobile phase: 10-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 5 min.) retention time=2.472 min.

Workup

  1. temperatureto cool to ambient temperature
  2. customdried under vacuum
  3. washFlash column chromatography (silica) was performed eluting with ethyl acetate to 20% MeOH/ethyl acetate

Sources & evidence

ORD record
ord-856f155894b246298bd7d9cc9e85795a
Source dataset
uspto-grants-2015_10
Patent number
US09163003B2

Reaction notes

Loading…