Sodium Carbonate → 2-Cyclopropyl-6-(trifluoromethyl)nicotinaldehyde

HRID 1626523Notes

Reaction equation

HRID 1626523 reaction equation
Cl[C:2]1[N:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[CH:14]1(B(O)O)[CH2:16][CH2:15]1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:14]1([C:2]2[N:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=2[CH:4]=[O:5])[CH2:16][CH2:15]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2760897Cyclopropylboronic acidHCID 467399062-Chloro-6-(trifluoromethyl)pyridine-3-carbaldehyde

Product 1

HCID 866644002-Cyclopropyl-6-(trifluoromethyl)nicotinaldehydeYield 71.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

2-Chloro-6-(trifluoromethyl)nicotinaldehyde (176 mg, 0.840 mmol), cyclopropylboronic acid (152 mg, 1.76 mmol), sodium carbonate (267 mg, 2.52 mmol) and tetrakis(triphenylphosphine)palladium (0) (48.5 mg, 0.0420 mmol) were combined, diluted with toluene (2 mL) and water (200 μL). The reaction vial was purged with argon, heated to 90° C. and stirred for 24 hours. The reaction was allowed to cool, loaded onto silica gel and eluted with 5% ethyl acetate/hexanes to 50% ethyl acetate/hexanes to yield 2-cyclopropyl-6-(trifluoromethyl)nicotinaldehyde (130 mg, 0.604 mmol, 71.9% yield).

Workup

  1. customThe reaction
  2. customvial was purged with argon
  3. temperatureto cool
  4. washeluted with 5% ethyl acetate/hexanes to 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-2e9856b3cd7545e098d45477bcf06e59
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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