Ethanol → Ethyl 5-chloronicotinate

HRID 2250638Notes

Reaction equation

HRID 2250638 reaction equation
[CH2:1]([OH:3])[CH3:2].CN([CH:7]=[O:8])C.C(P(C1C=CC=CC=1)C1C=CC=CC=1)CCP(C1C=CC=CC=1)C1C=CC=CC=1.FC(F)(F)S(O[C:44]1[CH:45]=[N:46][CH:47]=[C:48]([Cl:50])[CH:49]=1)(=O)=O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCN(CC)CC>[Cl:50][C:48]1[CH:47]=[N:46][CH:45]=[C:44]([CH:49]=1)[C:7]([O:3][CH2:1][CH3:2])=[O:8]

Participants

7

Reactant 4

HCID 702EthanolHCID 6228DimethylformamideHCID 812191,3-Bis(diphenylphosphino)propaneHCID 151858705-Chloropyridin-3-yl trifluoromethanesulfonate

Product 1

HCID 210009Ethyl 5-chloronicotinate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

To ethanol (66 mL) and DMF (66 mL) was added Et3N (29.4 mL), 1,3-propanediylbis(diphenylphosphine) (3.48 g) and palladium acetate (1.9 g) in ice-water bath. To this was added 5-chloro-3-pyridinyl trifluoromethanesulfonate (22.1 g) at the temperature. The mixture was stirred at 50° C. for 4 hours under CO (1 atom). The mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc. The combined organic layer was washed with water three times, dried over MgSO4 and evaporated in vacuo. The residue was purified by silica gel column chromatography (silica gel, 200 mL) eluted with hexane-EtOAc=15-1 and 10-1 to give ethyl 5-chloronicotinate (105 g) as a pale brown oil.

Workup

  1. customThe mixture was partitioned between EtOAc and water
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washThe combined organic layer was washed with water three times
  4. dry with materialdried over MgSO4
  5. customevaporated in vacuo
  6. customThe residue was purified by silica gel column chromatography (silica gel, 200 mL)
  7. washeluted with hexane-EtOAc=15-1 and 10-1

Sources & evidence

ORD record
ord-9bf3a49e8da544f3bdbb93e94ceb3021
Source dataset
uspto-grants-2008_01
Patent number
US07317009B2

Reaction notes

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