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

HRID 1803957노트

반응식

HRID 1803957 반응식
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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-3096257f4bd545d9b00311d3bb06d852
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08354401B2

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