1-(2-Hydroxyethyl)piperazine → N-(2,4-dichloro-6-methylpyridin-3-yl)-2-[4-(2-hydroxyethyl)piperazin-1-yl]acetamide

HRID 348582Notes

Reaction equation

HRID 348582 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][C:9](=[O:12])[CH2:10]Br)=[C:6]([Cl:13])[CH:5]=[C:4]([CH3:14])[N:3]=1.C(=O)([O-])[O-].[K+].[K+].[OH:21][CH2:22][CH2:23][N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1>C(#N)C>[Cl:1][C:2]1[C:7]([NH:8][C:9](=[O:12])[CH2:10][N:27]2[CH2:28][CH2:29][N:24]([CH2:23][CH2:22][OH:21])[CH2:25][CH2:26]2)=[C:6]([Cl:13])[CH:5]=[C:4]([CH3:14])[N:3]=1

Participants

5

Reactant 3

HCID 76771-(2-Hydroxyethyl)piperazineHCID 11430Potassium CarbonateHCID 10266671N-(2,4-dichloro-6-methylpyridin-3-yl)-2-bromoacetamide

Product 1

HCID 10020570N-(2,4-dichloro-6-methylpyridin-3-yl)-2-[4-(2-hydroxyethyl)piperazin-1-yl]acetamideYield 90.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
5 °C

Procedure

N-(2,4-Dichloro-6-methylpyridin-3-yl)-2-bromoacetamide (70.0 g, 234.9 mmol) was dissolved in acetonitrile (105 mL), and potassium carbonate (39.0 g, 282.2 mmol) was added to the solution under stirring and under cooling with ice. While the inner temperature was maintained at 5° C. or lower, a solution of 1-(2-hydroxyethyl)piperazine (36.7 g, 281.9 mmol) in acetonitrile (140 mL) was added dropwise to the resultant mixture. Thereafter, the temperature of the mixture was elevated to room temperature, and the mixture was stirred for 4 hours. The reaction mixture was extracted with chloroform-water, and the aqueous layer was further extracted twice with chloroform. The combined organic layer was washed with saturated brine and dried over sodium sulfate anhydrate, followed by condensation under reduced pressure. The residue was recrystallized from isopropanol and diisopropyl ether, to thereby yield 73.57 g of N-(2,4-dichloro-6-methylpyridin-3-yl)-2-[4-(2-hydroxyethyl)piperazin-1-yl]acetamide (yield: 90%) as colorless crystals.

Workup

  1. temperatureunder cooling with ice
  2. customwas elevated to room temperature
  3. stirringthe mixture was stirred for 4 hours
  4. extractionThe reaction mixture was extracted with chloroform-water
  5. extractionthe aqueous layer was further extracted twice with chloroform
  6. washThe combined organic layer was washed with saturated brine
  7. dry with materialdried over sodium sulfate anhydrate
  8. customfollowed by condensation under reduced pressure
  9. customThe residue was recrystallized from isopropanol and diisopropyl ether

Sources & evidence

ORD record
ord-bc59b480a44c4dab964aed26537cc76c
Source dataset
uspto-grants-2007_02
Patent number
US07176306B2

Reaction notes

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