2-Bromo-5-(trifluoromethyl)pyridine → HCID 57917724, compound

HRID 2110131Notes

Reaction equation

HRID 2110131 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][C:10](C)([C:14]([OH:16])=[O:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][N:20]=1.[Cl-].[CH2:30](C1C=CC=C(CCC)C=1[N+]1C=CN(C2C(CCC)=CC=CC=2CCC)C=1)CC.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[CH3:30][O:16][C:14]([CH:10]1[N:11]([C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][N:20]=2)[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]1)=[O:15]

Participants

6

Reactant 4

HCID 27364342-Bromo-5-(trifluoromethyl)pyridineHCID 223147471,3-Bis(2,6-di-1-propylphenyl)imidazolium chlorideHCID 23676156Sodium t-butoxideHCID 670459621189435-14-0

Product 1

HCID 57917724HCID 57917724, compoundYield 282.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

3-Methyl-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester (120 mg, 0.49 mmol) and 2-Bromo-5-trifluoromethyl-pyridine (133 mg, 0.59 mmol) were dissolved in 2.0 mL of anhydrous toluene (degassed). In a separate, septum-equipped vial were placed tri(dibenzylideneacetone)dipalladium (0) (22 mg, 0.024 mmol), 1,3-bis(2,6-di-1-propylphenyl)imidazolium chloride (42 mg, 0.1 mmol) and sodium t-butoxide (57 mg, 0.59 mmol). This “catalytic” vial was equipped with a magnetic stir bar and flushed with dry nitrogen. The reactant solution was next transferred to the “catalytic” vial and the mixture was stirred at 100° C. for 5 h. After this period the mixture was combined with 20 mL of hexane/EtOAc (2:1) and was passed through a pad of Celite. The resulting filtrate was evaporated in vacuo and purified using flash silica chromatography (0-20% EtOAc/Hexane) to yield 110 mg (58%) of 4-(5-Trifluoromethyl-pyridin-2-yl)-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester.

Workup

  1. customIn a separate, septum-equipped vial
  2. customThis “catalytic” vial was equipped with a magnetic stir bar
  3. customflushed with dry nitrogen
  4. waitAfter this period the mixture was combined with 20 mL of hexane/EtOAc (2:1)
  5. customThe resulting filtrate was evaporated in vacuo
  6. custompurified

Sources & evidence

ORD record
ord-c2efb4c28c69433da6807e3a45eda2a4
Source dataset
uspto-grants-2009_04
Patent number
US07517884B2

Reaction notes

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