4-(3-Methyl-5-vinylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester → 4-(5-Ethyl-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester

HRID 2411207Notes

Reaction equation

HRID 2411207 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([CH3:20])=[CH:18][C:17]([CH:21]=[CH2:22])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)C>[C:1]([O:5][C:6]([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:7])([CH3:4])([CH3:3])[CH3:2]

Participants

3

Reactant 1

HCID 673806954-(3-Methyl-5-vinylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 673812894-(5-Ethyl-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl esterYield 66.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

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 stirred with heating under reflux for 8 hr. The reaction mixture was cooled, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The obtained 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). The obtained 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 at room temperature for 8 hr under hydrogen atmosphere. The mixture was filtered through celite, and the solvent was evaporated from the filtrate to give 4-(5-ethyl-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (870 mg). The obtained 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. To the reaction mixture was added 1N aqueous sodium hydroxide solution (7 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 (441 mg).

Workup

  1. addition5% palladium carbon-ethylenediamine complex (600 mg) was added
  2. filtrationThe mixture was filtered through celite
  3. customthe solvent was evaporated from the filtrate

Sources & evidence

ORD record
ord-806219b4e8a44c7dac6b3a53c9b82dff
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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