Tetrahydrofuran → [4-(2-Cyclopropyl-4-methylphenyl)piperazin-1-yl](4-iodophenyl)methanone

HRID 1803957Notes

Reaction equation

HRID 1803957 reaction equation
O1CCCC1.[I:6][C:7]1[CH:15]=[CH:14][C:10]([C:11](Cl)=[O:12])=[CH:9][CH:8]=1.Cl.[CH:17]1([C:20]2[CH:25]=[C:24]([CH3:26])[CH:23]=[CH:22][C:21]=2[N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)[CH2:19][CH2:18]1.[OH-].[Na+]>C(OCC)(=O)C>[CH:17]1([C:20]2[CH:25]=[C:24]([CH3:26])[CH:23]=[CH:22][C:21]=2[N:27]2[CH2:32][CH2:31][N:30]([C:11]([C:10]3[CH:14]=[CH:15][C:7]([I:6])=[CH:8][CH:9]=3)=[O:12])[CH2:29][CH2:28]2)[CH2:18][CH2:19]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 743734-Iodobenzoyl chlorideHCID 673813981-(2-Cyclopropyl-4-methylphenyl)piperazine hydrochloride

Product 1

HCID 58484789[4-(2-Cyclopropyl-4-methylphenyl)piperazin-1-yl](4-iodophenyl)methanoneYield 99.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 4-(2-chloro-4-methylphenyl)piperazine-1-carboxylic acid tert-butyl ester (932 mg), bis(tricyclohexylphosphine)palladium (II) dichloride (132 mg), tripotassium phosphate (3.8 g) and cyclopropylboronic acid (688 mg) were added toluene (10 mL) and water (500 μL) and the mixture was refluxed for 5 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 (chloroform) to give 4-(2-cyclopropyl-4-methylphenyl)piperazine-1carboxylic acid tert-butyl ester (1 g). 4-(2-Cyclopropyl-4-methylphenyl)piperazine-1carboxylic acid tert-butyl ester (1 g) was dissolved in chloroform (1 mL), 4N hydrogen chloride/ethyl acetate (1 mL) was added, and the mixture was stirred at room temperature for 3 hr. Filtration gave 1-(2-cyclopropyl-4-methylphenyl)piperazine hydrochloride (160 mg). To tetrahydrofuran (2 mL) were added 4-iodobenzoyl chloride (169 mg), 1-(2-cyclopropyl-4-methylphenyl)piperazine hydrochloride (160 mg) and 1N aqueous sodium hydroxide solution (2 mL), and the mixture was stirred at room temperature overnight. Ethyl acetate was added for partitioning, the organic layer was washed with saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (chloroform) to give the title compound (280 mg).

Workup

  1. customfor partitioning
  2. washthe organic layer was washed with saturated brine
  3. customthe solvent was evaporated
  4. customThe residue was purified by column chromatography (chloroform)

Sources & evidence

ORD record
ord-3096257f4bd545d9b00311d3bb06d852
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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