Sodium Hydroxide → 1-(3-Methyl-5-propylpyridin-2-yl)piperazine

HRID 1804053Notes

Reaction equation

HRID 1804053 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([CH3:20])=[CH:18][C:17]([CH2:21][CH2:22][CH3:23])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.C(OCC)(=O)C.[OH-].[Na+]>C(Cl)(Cl)Cl>[CH3:20][C:19]1[C:14]([N:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[N:15][CH:16]=[C:17]([CH2:21][CH2:22][CH3:23])[CH:18]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 21866389Hydrogen chloride-ethyl acetateHCID 673811674-[3-Methyl-5-propylpyridin-2-yl]piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 584844921-(3-Methyl-5-propylpyridin-2-yl)piperazineYield 70.4%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a mixture of 4-(5-bromo-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (6.7 g), bis(tricyclohexylphosphine)palladium (II) dichloride (148 mg), tripotassium phosphate (13 g) and cis-1-propene-1-boronic acid (2.6 g) were added toluene (60 mL) and water (3 mL), and the mixture was refluxed for 8 hr. After cooling, the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (hexane:ethyl acetate) to give 4-[3-methyl-5-propenylpyridin-2-yl]piperazine-1-carboxylic acid tert-butyl ester (6 g). 4-[3-Methyl-5-propenylpyridin-2-yl]piperazine-1-carboxylic acid tert-butyl ester (6 g) was dissolved in ethanol (40 mL), 5% palladium carbon-ethylenediamine complex (1.2 g) was added, and the mixture was stirred under a hydrogen atmosphere at room temperature overnight. After celite filtration, the solvent in the filtrate was evaporated to give 4-[3-methyl-5-propylpyridin-2-yl]piperazine-1-carboxylic acid tert-butyl ester (6 g). 4-[3-Methyl-5-propylpyridin-2-yl]piperazine-1-carboxylic acid tert-butyl ester (6 g) was dissolved in chloroform (10 mL), 4N hydrogen chloride/ethyl acetate (10 mL) was added, and the mixture was stirred at room temperature overnight. To the reaction mixture was added 1N aqueous sodium hydroxide solution (40 mL), and the mixture was extracted with chloroform. The organic layer was washed with saturated brine, and the solvent was evaporated to give the title compound (2.9 g).

Workup

  1. extractionthe mixture was extracted with chloroform
  2. washThe organic layer was washed with saturated brine
  3. customthe solvent was evaporated

Sources & evidence

ORD record
ord-1edefaed5ca4472abd92870828ef4d8e
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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