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

HRID 1803982Notes

Reaction equation

HRID 1803982 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.C(Cl)(Cl)Cl.C(=O)([O-])[O-].[K+].[K+]>O>[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 6212ChloroformHCID 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 962WaterSolvent

Procedure

To 2,3,5-trichloropyridine (25 g) were added 1-BOC-piperazine (28.13 g), potassium carbonate (37.86 g), 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 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 4-(3,5-dichloropyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (6.35 g) were added palladium (II) acetate (0.46 g), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (1.71 g), potassium fluoride (9.556 g), methylboronic acid (5 g) and tetrahydrofuran (202 mL), and the mixture was refluxed under a nitrogen stream for 8 hr. 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 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). To 4-(3,5-dimethylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (5.45 g) were added 4N hydrogen chloride/ethyl acetate (18.2 mL) and chloroform (45.5 mL), and the mixture was stirred at room temperature. After completion of the reaction, to the reaction mixture were added water and potassium carbonate, and the mixture was extracted with ethyl acetate. 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-c9ac8e50a4804ae9a655c5ace23e9326
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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