Sodium Hydroxide → 1-(5-Cyclobutyl-3-methylpyridin-2-yl)piperazine
Reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([CH3:20])=[CH:18][C:17]([CH:21]3[CH2:24][CH2:23][CH2:22]3)=[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>[CH:21]1([C:17]2[CH:18]=[C:19]([CH3:20])[C:14]([N:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)=[N:15][CH:16]=2)[CH2:22][CH2:23][CH2:24]1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a mixture of 4-(5-bromo-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (4.8 g), bis(tricyclohexylphosphine)palladium (II) dichloride (515 mg), tripotassium phosphate (16 g) and cyclobutylboronic acid (2.6 g) were added toluene (39 mL) and water (2 mL), and the mixture was refluxed for 8 hr. After cooling, the mixture was extracted with ethyl acetate, washed with saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (hexane:ethyl acetate) to give 4-(5-cyclobutyl-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (560 mg). 4-(5-cyclobutyl-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (560 mg) was dissolved in chloroform (1.5 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 (8 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 (350 mg).
Workup
- extractionthe mixture was extracted with chloroform
- washThe organic layer was washed with saturated brine
- customthe solvent was evaporated
Sources & evidence
- ORD record
- ord-094bdb9fd6974caa8f53ee3ce68292a0
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08354401B2
Reaction notes
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