Nitrogen → Ethyl 6-propylpicolinate

HRID 1048501Notes

Reaction equation

HRID 1048501 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:5]=[CH:4][CH:3]=1.N#N.[Br-].[CH2:16]([Zn+])[CH2:17][CH3:18]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:16]([C:2]1[N:7]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:5]=[CH:4][CH:3]=1)[CH2:17][CH3:18]

Participants

6

Reactant 3

HCID 947NitrogenHCID 2758810Ethyl 6-BromopicolinateHCID 178455869HCID 178455869, compound

Product 1

HCID 68000588Ethyl 6-propylpicolinate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of ethyl 6-bromopicolinate (8 g, 34.8 mmol, purchased from AK Scientific, Inc., Union City, Calif.) in THF (200 mL) was sparged with N2 at 0° C. for 20 min. To the mixture under N2 atmosphere was added Pd(PPh3)4 (3.21 g, 2.78 mmol) and a solution of propylzinc bromide (100 mL, 0.5 M in THF, 50.0 mmol) dropwise over 30 min. The mixture was removed from the ice bath and heated to reflux for 18 h. After that time the solution was cooled to rt, poured into saturated aqueous NH4Cl solution (18 mL), diluted with water (30 mL), and extracted with EtOAc (3×30 mL). The combined organic layers were washed with water and sat. aq. NaCl solution and were dried over Na2SO4. After removal of the organic solvents under reduced pressure, purification of the residue by flash chromatography on silica gel with 0 to 50% EtOAc/hexanes provided the title compound. Mass Spectrum (ESI) m/z=194.0 (M+1).

Workup

  1. customThe mixture was removed from the ice bath
  2. temperatureheated
  3. temperatureto reflux for 18 h
  4. additionpoured into saturated aqueous NH4Cl solution (18 mL)
  5. additiondiluted with water (30 mL)
  6. extractionextracted with EtOAc (3×30 mL)
  7. washThe combined organic layers were washed with water and sat. aq. NaCl solution
  8. dry with materialwere dried over Na2SO4
  9. customAfter removal of the organic solvents
  10. customunder reduced pressure, purification of the residue by flash chromatography on silica gel with 0 to 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-8a507ea5aa9740f79cbe7cf128ceee25
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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