Ethyl Acetate → 2-(4-Benzyl-piperazin-1-yl)-N-methyl-acetamide

HRID 1972726

Reaction equation

HRID 1972726 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:15][C:16]([NH:18][CH3:19])=[O:17].C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([CH2:15][C:16]([NH:18][CH3:19])=[O:17])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 667732-chloro-N-methylacetamideHCID 759941-Benzylpiperazine

Product 1

HCID 368452302-(4-Benzyl-piperazin-1-yl)-N-methyl-acetamideYield 83%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 1-benzyl-piperazine (1.0 g, 5.67 mmol), 2-chloro-N-methylacetamide (671.2 mg, 6.24 mmol, 1.1 eq.), and potassium carbonate (941 mg, 6.81 mmol, 1.2 eq.) in anhydrous THF (23 mL) was stirred at 60° C. under N2 for 18 h. The mixture was cooled to rt and poured into EtOAc. The organic phase was washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by MPLC (Biotage®, gradient elution 1:4:5 v/v MeOH:Acetone:DCM) to give 1.16 g (83%) of the product as a white solid. 1H-NMR (300 MHz, DMSO-d6) 7.62 to 7.56 (broad d, 1H), 7.33 to 7.20 (m, 5H), 3.45 (s, 2H), 2.85 (s, 2H), 2.58 (d, 3H), 2.44 to 2.33 (broad s, 8H); ES-MS m/z 248.2 [M+H]+, RT (min) 0.33.

Workup

  1. temperatureThe mixture was cooled to rt
  2. washThe organic phase was washed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by MPLC (Biotage®, gradient elution 1:4:5 v/v MeOH:Acetone:DCM)

Sources & evidence

ORD record
ord-3cf0cccfa4de48788a451027f19e9182
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Linked notes

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