Sodium Hydroxide → 1-(5-Ethyl-3-methylpyridin-2-yl)piperazine

HRID 1803999Notes

Reaction equation

HRID 1803999 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][CH3:22])=[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>[CH2:21]([C:17]1[CH:18]=[C:19]([CH3:20])[C:14]([N:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[N:15][CH:16]=1)[CH3:22]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 21866389Hydrogen chloride-ethyl acetateHCID 673812894-(5-Ethyl-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 584845781-(5-Ethyl-3-methylpyridin-2-yl)piperazineYield 75.4%

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 (3.3 g), bis(tricyclohexylphosphine)palladium (II) dichloride (332 mg), tripotassium phosphate (11 g) and vinylboronic acid pinacol ester (3 g) were added toluene (27 mL) and water (1.4 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-vinylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (1.3 g). 4-(3-Methyl-5-vinylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (1.3 g) was dissolved in ethanol (20 mL), 5% palladium carbon-ethylenediamine complex (600 mg) was added, and the mixture was stirred under a hydrogen atmosphere for 8 hr at room temperature. After celite filtration, the solvent in the filtrate was evaporated to give 4-(5-ethyl-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (870 mg). 4-(5-Ethyl-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (870 mg) was dissolved in chloroform (2 mL), 4N hydrogen chloride/ethyl acetate (1.5 mL) was added, and the mixture was stirred at room temperature overnight. 1N Aqueous sodium hydroxide solution (7 mL) was added, 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 (441 mg).

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-d28d7b1e26984cad8a345889c2632e03
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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