Water → 1-(3,5-Dimethylpyridin-2-yl)piperazine

HRID 2411203Notes

Reaction equation

HRID 2411203 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([CH3:20])=[CH:18][C:17]([CH3:21])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.C(OCC)(=O)C.O.C(=O)([O-])[O-].[K+].[K+]>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]([CH3:21])[CH:18]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 21866389Hydrogen chloride-ethyl acetateHCID 673812824-(3,5-Dimethylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 584844961-(3,5-Dimethylpyridin-2-yl)piperazineYield 92.2%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a mixture of 2,3,5-trichloropyridine (25 g), 1-Boc-piperazine (28.13 g) and potassium carbonate (37.86 g) were added N,N-dimethylformamide (25 mL) and toluene (50 mL), and the mixture was stirred at 100° C. After completion of the reaction, water was added to the reaction mixture, 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-(3,5-dichloropyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (39.13 g). To a mixture of the obtained 4-(3,5-dichloropyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (6.35 g), palladium(II) acetate (0.46 g), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (1.71 g), potassium fluoride (9.56 g) and methylboronic acid (5 g) was added tetrahydrofuran (202 mL), and the mixture was stirred with heating under reflux for 8 hr under a nitrogen stream. Water was added to the reaction mixture, 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-(3,5-dimethylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (5.45 g). The obtained 4-(3,5-dimethylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (5.45 g) was dissolved in chloroform (46 mL), 4N hydrogen chloride/ethyl acetate (18 ml) was added, and the mixture was stirred at room temperature. After completion of the reaction, to the reaction mixture were added water and potassium carbonate, the mixture was extracted with ethyl acetate, and the solvent was evaporated to give the title compound (3.3 g).

Workup

  1. customAfter completion of the reaction
  2. extractionthe mixture was extracted with ethyl acetate
  3. customthe solvent was evaporated

Sources & evidence

ORD record
ord-67436b5ff88d4541ac394dddd9a9d73a
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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