Tetrahydrofuran → HCID 71251889, compound

HRID 2411238Notes

Reaction equation

HRID 2411238 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([C:20]#[N:21])=[CH:18][C:17](Br)=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:23]B(O)O.[F-].[K+].O1CCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([C:20]#[N:21])=[CH:18][C:17]([CH3:23])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 139377Methylboronic AcidHCID 522689Potassium FluorideHCID 66524905HCID 66524905, compound

Product 1

HCID 71251889HCID 71251889, compoundYield 108.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 962WaterSolvent

Procedure

Under a nitrogen stream, to a mixture of 4-(5-bromo-3-cyanopyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (1.52 g) described in Preparation Example 105, methylboronic acid (0.50 g), palladium(II) acetate (46 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.17 g) and potassium fluoride (0.96 g) was added tetrahydrofuran (40 mL), and the mixture was stirred with heating under reflux for 8 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate) to give the title compound (1.36 g).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 8 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. customthe solvent was evaporated
  6. customThe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-5db5ff3d587c408d8997ed0186d503fa
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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