Potassium Phosphate, Tribasic → 4-(5-Cyclopropylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester

HRID 1804130Notes

Reaction equation

HRID 1804130 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[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:29]1(B(O)O)[CH2:31][CH2:30]1.C(=O)([O-])O.[Na+]>C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.[Cl-].[Cl-].[Pd+2].C(OCC)(=O)C.O.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([CH:29]3[CH2:31][CH2:30]3)=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 516892Sodium BicarbonateHCID 2760897Cyclopropylboronic acidHCID 112447754-Boc-1-(5-bromo-2-pyridyl)piperazine

Product 1

HCID 673810174-(5-Cyclopropylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl esterYield 71.6%

Reagents, catalysts & solvents 4

HCID 11556747Bis(tricyclohexylphosphine)palladium(II) DichlorideCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 4-(5-bromopyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (5.37 g), bis(tricyclohexylphosphine)palladium (II) dichloride (347 mg), tripotassium phosphate (9.99 g) and cyclopropylboronic acid (2.02 g) were added toluene (49 mL) and water (2.5 mL), and the mixture was refluxed. After cooling, ethyl acetate and saturated aqueous sodium hydrogen carbonate solution were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate, and the solvent was evaporated. The residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound (3.41 g).

Workup

  1. temperaturethe mixture was refluxed
  2. temperatureAfter cooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over sodium sulfate
  6. customthe solvent was evaporated
  7. customThe residue was purified by column chromatography (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-ebaef89e85eb4d81a52e4d8aa0e3208d
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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