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

HRID 1804002ノート

反応式

HRID 1804002 の反応式
[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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 11556747Bis(tricyclohexylphosphine)palladium(II) Dichloride触媒HCID 962Water溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-7ce875a981d945d4af3c13d85682da8d
出典データセット
uspto-grants-2013_01
特許番号
US08354401B2

反応ノート

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