Water → Ethyl 5-chloro-2-methylnicotinate

HRID 660249Notes

Reaction equation

HRID 660249 reaction equation
Cl[C:2]1[N:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].[CH3:14]B1OB(C)OB(C)O1.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1>[Cl:13][C:10]1[CH:11]=[N:12][C:2]([CH3:14])=[C:3]([CH:9]=1)[C:4]([O:6][CH2:7][CH3:8])=[O:5]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 5200405Ethyl 2,5-dichloronicotinate

Product 1

HCID 53396281Ethyl 5-chloro-2-methylnicotinateYield 37,958.301%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of ethyl 2,5-dichloronicotinate (step 1, 10 g, 0.045 mol), tetrakis(triphenylphoshine)palladium (5.2 g, 4.5 mmol), trimethylboroxine (5.65 g, 0.045 mmol) and potassium carbonate (18.66 g, 0.16 mmol) in 1,4-dioxane (contain 10% water, 100 ml) was refluxed for 7 h under nitrogen atmosphere. The reaction mixture was cooled to room temperature and poured into water. The aqueous mixture was extracted with ethyl acetate. The organic extracts were dried over sodium sulfate and concentrated. The residue was purified by flush column chromatography on silica gel eluting with hexane/ethyl acetate (50/1 to 20/1) to afford 3.41 g (38%) of the title compound:

Workup

  1. temperaturewas refluxed for 7 h under nitrogen atmosphere
  2. extractionThe aqueous mixture was extracted with ethyl acetate
  3. dry with materialThe organic extracts were dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified
  6. customby flush column chromatography on silica gel eluting with hexane/ethyl acetate (50/1 to 20/1)

Sources & evidence

ORD record
ord-e2306f648d474219bbc3751984273017
Source dataset
uspto-grants-2011_12
Patent number
US08084476B2

Reaction notes

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