6-Bromonicotinic acid → (6-Bromopyridin-3-yl)[4-(2,4,5-trimethylphenyl)piperazin-1-yl]methanone

HRID 1804094Notes

Reaction equation

HRID 1804094 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.[CH3:11][C:12]1[CH:17]=[C:16]([CH3:18])[C:15]([CH3:19])=[CH:14][C:13]=1[N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1>>[Br:1][C:2]1[N:3]=[CH:4][C:5]([C:6]([N:23]2[CH2:24][CH2:25][N:20]([C:13]3[CH:14]=[C:15]([CH3:19])[C:16]([CH3:18])=[CH:17][C:12]=3[CH3:11])[CH2:21][CH2:22]2)=[O:8])=[CH:9][CH:10]=1

Participants

3

Reactant 2

HCID 2389326-Bromonicotinic acidHCID 27608211-(2,4,5-Trimethylphenyl)piperazine

Product 1

HCID 58484642(6-Bromopyridin-3-yl)[4-(2,4,5-trimethylphenyl)piperazin-1-yl]methanoneYield 101%

Procedure

To a mixture of 1-Boc-piperazine (1.39 g), 1-bromo-2,4,5-trimethylbenzene (1 g), tris(dibenzylideneacetone)dipalladium (0) (257 mg), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (481 mg) and sodium tert-butoxide (669 mg) was added toluene (10 mL), and the mixture was refluxed for 3 hr. After cooling, 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 (ethyl acetate:hexane) to give 4-(2,4,5-trimethylphenyl)piperazine-1-carboxylic acid tert-butyl ester (1.53 g). 4-(2,4,5-trimethylphenyl)piperazine-1-carboxylic acid tert-butyl ester (1.53 g) was dissolved in dichloromethane (10 mL), 4N hydrogen chloride/dioxane (5 mL) was added, and the mixture was stirred at room temperature for 3 hr. Diethyl ether (100 mL) was added, and the precipitate was collected by filtration. To the obtained precipitate were added ethyl acetate and 1N aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate and washed with saturated brine. The solvent was evaporated to give 1-(2,4,5-trimethylphenyl)piperazine (920 mg). By reaction and treatment in the same manner as in Preparation Example 27 and using 6-bromonicotinic acid (412 mg) and 1-(2,4,5-trimethylphenyl)piperazine (440 mg), the title compound (800 mg) was obtained.

Workup

  1. customBy reaction and treatment in the same manner
  2. customas in Preparation Example 27

Sources & evidence

ORD record
ord-d529b43e7a1040cf82481de6857d5901
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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