Methylboronic Acid → tert-Butyl 4-(5-methylpyridin-2-yl)piperazine-1-carboxylate

HRID 1804127Notes

Reaction equation

HRID 1804127 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].[CH:21]1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[F-].[K+].CB(O)O>[Cl-].[Na+].O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([CH3:21])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 139377Methylboronic AcidHCID 522689Potassium FluorideHCID 112447754-Boc-1-(5-bromo-2-pyridyl)piperazineHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl

Product 1

HCID 45788994tert-Butyl 4-(5-methylpyridin-2-yl)piperazine-1-carboxylateYield 910.3%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a mixture of 4-(5-bromopyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (5.33 g), palladium (II) acetate (175 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (639 mg), potassium fluoride (5.43 g) and methylboronic acid (2.80 g) was added tetrahydrofuran (120 mL), and the mixture was refluxed under a nitrogen stream for 3 hr. To the reaction mixture were added ethyl acetate and saturated brine, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound (3.93 g).

Workup

  1. temperaturethe mixture was refluxed under a nitrogen stream for 3 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by column chromatography (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-6fc46037091c4648b0c8dd57dbf42181
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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