Ethyl Acetate → 1-(3-Cyclopropyl-5-methylpyridin-2-yl)piperazine hydrochloride

HRID 2411214Notes

Reaction equation

HRID 2411214 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([CH:20]3[CH2:22][CH2:21]3)=[CH:18][C:17]([CH3:23])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:24].C(OCC)(=O)C.C(OCC)(=O)C>C(Cl)(Cl)Cl>[ClH:24].[CH:20]1([C:19]2[C:14]([N:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)=[N:15][CH:16]=[C:17]([CH3:23])[CH:18]=2)[CH2:21][CH2:22]1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 21866389Hydrogen chloride-ethyl acetateHCID 49871665Tert-butyl 4-(3-cyclopropyl-5-methylpyridin-2-yl)piperazine-1-carboxylate

Product 1

HCID 673807751-(3-Cyclopropyl-5-methylpyridin-2-yl)piperazine hydrochloride

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

bis(tricyclohexylphosphine)palladium(II)dichloride (1 g), tripotassium phosphate (30 g) and cyclopropylboronic acid (5.5 g) were added toluene (80 mL) and water (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-cyclopropyl-5-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (9 g). The obtained 4-(3-cyclopropyl-5-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (9 g) was dissolved in chloroform (25 mL), 4N hydrogen chloride/ethyl acetate (25 mL) was added, and the mixture was stirred at room temperature overnight. To the reaction mixture was added ethyl acetate (100 mL), and the precipitate was collected by filtration to give the title compound (4.6 g).

Workup

  1. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-be87ae5fdad64c259fae7353c6d3b81c
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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