Toluene → 4-(5-Cyclobutyl-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester

HRID 1804002노트

반응식

HRID 1804002 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([CH3:20])=[CH:18][C:17](Br)=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH:30]1(B(O)O)[CH2:33][CH2:32][CH2:31]1.C1(C)C=CC=CC=1>C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.[Cl-].[Cl-].[Pd+2].O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([CH3:20])=[CH:18][C:17]([CH:30]3[CH2:33][CH2:32][CH2:31]3)=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 16217845Cyclobutylboronic acidHCID 46739269tert-Butyl 4-(5-bromo-3-methylpyridin-2-yl)piperazine-1-carboxylate

생성물 1

HCID 673809704-(5-Cyclobutyl-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester수율 12.5%

시약·촉매·용매 2

HCID 11556747Bis(tricyclohexylphosphine)palladium(II) Dichloride촉매HCID 962Water용매

실험 절차

To a mixture of 4-(5-bromo-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (4.8 g), bis(tricyclohexylphosphine)palladium (II) dichloride (515 mg), tripotassium phosphate (16 g) and cyclobutylboronic acid (2.6 g) were added toluene (39 mL) and water (2 mL), and the mixture was refluxed for 8 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 (hexane:ethyl acetate) to give 4-(5-cyclobutyl-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (560 mg). 4-(5-cyclobutyl-3-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (560 mg) was dissolved in chloroform (1.5 mL), 4N hydrogen chloride/ethyl acetate (1.5 mL) was added, and the mixture was stirred at room temperature overnight. To the reaction mixture was added 1N aqueous sodium hydroxide solution (8 mL), and the mixture was extracted with chloroform. The organic layer was washed with saturated brine, and the solvent was evaporated to give the title compound (350 mg).

후처리

  1. temperaturethe mixture was refluxed for 8 hr
  2. temperatureAfter cooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. washwashed with saturated brine
  5. customthe solvent was evaporated
  6. customThe residue was purified by column chromatography (hexane:ethyl acetate)

출처 및 근거

ORD 기록
ord-7ce875a981d945d4af3c13d85682da8d
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08354401B2

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