Acetonitrile → 4-((6-Chloropyridin-3-yl)methyl)piperazin-2-one

HRID 79211Notes

Reaction equation

HRID 79211 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8]Cl)=[CH:4][N:3]=1.[NH:10]1[CH2:15][CH2:14][NH:13][CH2:12][C:11]1=[O:16].C(=O)([O-])[O-].[K+].[K+].C(#N)C>C1COCC1>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([CH2:8][N:13]2[CH2:14][CH2:15][NH:10][C:11](=[O:16])[CH2:12]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 1554792-Chloro-5-(chloromethyl)pyridineHCID 231360Piperazin-2-one

Product 1

HCID 201122834-((6-Chloropyridin-3-yl)methyl)piperazin-2-oneYield 34.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-chloro-5-(chloromethyl)pyridine (1.4 g, 8.4 mmol), piperazinone (0.84 g, 8.4 mmol), and potassium carbonate (1.0 mL, 17 mmol) in a mixed solvent consisting of acetonitrile (40 mL) and THF (20 mL) was stirred at room temperature for 3.5 days. Upon workup, the mixture was filtered through a layer of celite and the cake was washed with ethyl acetate. The filtrate was concentrated in vacuo and the residue was subjected to combi-flash column chromatography (methanol/DCM) to give compound 356 (0.65 g, 34% yield) as an off-white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.35 (1 H, d, J=2.0 Hz), 7.81 (1 H, dd, J=8.1, 2.4 Hz), 7.76 (1 H, br. s.), 7.49 (1 H, d, J=8.3 Hz), 3.57 (2 H, s), 3.10-3.16 (2 H, m), 2.93 (2 H, s), 2.52-2.56 (2H, m). LCMS-ESI (POS), M/Z, M+1: Found 226.0.

Workup

  1. filtrationUpon workup, the mixture was filtered through a layer of celite and the cake
  2. washwas washed with ethyl acetate
  3. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-9655ec0951cf4d3582eef28e4a7bbb3c
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Reaction notes

Loading…