Hydrochloric Acid → Ethyl 4-chloro-2-ethylpyridine-3-carboxylate

HRID 630188Notes

Reaction equation

HRID 630188 reaction equation
Br[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([Cl:13])[CH:5]=[CH:4][N:3]=1.[CH2:14]([Zn]CC)[CH3:15].O.Cl>O1CCOCC1>[Cl:13][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([CH2:14][CH3:15])[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 59589350Ethyl 2-bromo-4-chloronicotinateHCID 178418750HCID 178418750, compound

Product 1

HCID 19902853Ethyl 4-chloro-2-ethylpyridine-3-carboxylateYield 63%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
40 °C

Procedure

Ethyl 2-bromo-4-chloropyridine-3-carboxylate (1.5 g, 5.7 mmol) was dissolved in anhydrous dioxane (45 mL). A solution of diethyl zinc (4.6 mL, 5.1 mmol, 1.1 M in toluene) was added dropwise, and then was added (1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium (62 mg, 85 mol). The mixture was heated at 40° C. overnight, and then water plus 1 N HCl were added. The reaction mixture was extracted 3 times with ethyl acetate. The combined organic phase was washed with brine and dried over sodium sulfate. After evaporation, the residue was dissolved in DCM and purified on silica gel using 0-15% hexane/ethyl acetate to afford ethyl 4-chloro-2-ethylpyridine-3-carboxylate (687 mg, 57% yield).

Workup

  1. extractionThe reaction mixture was extracted 3 times with ethyl acetate
  2. washThe combined organic phase was washed with brine
  3. dry with materialdried over sodium sulfate
  4. customAfter evaporation
  5. dissolutionthe residue was dissolved in DCM
  6. custompurified on silica gel using 0-15% hexane/ethyl acetate

Sources & evidence

ORD record
ord-a6dfe1e3e74b47e5be3ac21d8654f89b
Source dataset
uspto-grants-2016_04
Patent number
US09315521B2

Reaction notes

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