Potassium Phosphate, Tribasic → 4-cyclopropylpicolinonitrile

HRID 931124Notes

Reaction equation

HRID 931124 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]#[N:9])[CH:3]=1.[CH:10]1(B(O)O)[CH2:12][CH2:11]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCCC1>[CH:10]1([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([C:8]#[N:9])[CH:3]=2)[CH2:12][CH2:11]1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 6932834-Bromo-2-cyanopyridineHCID 2760897Cyclopropylboronic acid

Product 1

HCID 753556264-cyclopropylpicolinonitrileYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-bromopicolinonitrile (0.2 g, 1.1 mmol) in tetrahydrofuran were added cyclopropyl boronic acid (0.093 g, 1.1 mmol), and potassium phosphate tribasic (0.694 g, 3.2 mmol). The resulting reaction mixture was degassed with nitrogen for 10 minutes and then added Pd(OAc)2 and S-phos were added. The reaction mixture was heated at reflux for 16 h, then was diluted with water and extracted with ethyl acetate. The organic layer was concentrated under reduced pressure and the residue was purified via flash chromatography (10% ethyl acetate in petroleum ether) to afford 4-cyclopropylpicolinonitrile (0.1 g, 70%). MS (ES+APCI) (M+H) 145.2; LCMS retention time 3.02 min (Method J).

Workup

  1. customThe resulting reaction mixture
  2. customwas degassed with nitrogen for 10 minutes
  3. additionadded Pd(OAc)2 and S-phos were added
  4. temperatureThe reaction mixture was heated
  5. temperatureat reflux for 16 h
  6. additionwas diluted with water
  7. extractionextracted with ethyl acetate
  8. concentrationThe organic layer was concentrated under reduced pressure
  9. customthe residue was purified via flash chromatography (10% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-b1f529bf285e495ba1537981c9778d6f
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

Loading…