Potassium Carbonate → Methyl 5-fluoro-2-methylnicotinate

HRID 660240Notes

Reaction equation

HRID 660240 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]([F:12])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH3:13]B(O)O.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1>[F:12][C:9]1[CH:10]=[N:11][C:2]([CH3:13])=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 139377Methylboronic AcidHCID 24229209Methyl 2-chloro-5-fluoronicotinate

Product 1

HCID 68863106Methyl 5-fluoro-2-methylnicotinateYield 70%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of methyl 2-chloro-5-fluoronicotinate (step 1, 1.5 g, 7.91 mmol), tetrakis(triphenylphoshine)palladium (914 mg, 0.79 mmol), methyboronic acid (521 mg, 8.70 mmol) and potassium carbonate (3.28 g, 23.7 mmol) in 1,4-dioxane (20 ml) was heated at 110° C. for 20 h under nitrogen atmosphere. The reaction mixture was filtered through a pad of celite (Celite™ (diatomaceous earth)) and the filtrate was concentrated. The residue was purified by flush column chromatography on silica gel eluting with hexane/ethyl acetate (20/1 to 4/1) to afford 936 mg (64%) of the title compound:

Workup

  1. filtrationThe reaction mixture was filtered through a pad of celite (Celite™ (diatomaceous earth))
  2. concentrationthe filtrate was concentrated
  3. customThe residue was purified
  4. customby flush column chromatography on silica gel eluting with hexane/ethyl acetate (20/1 to 4/1)

Sources & evidence

ORD record
ord-709f757fec5d4e24b155e4f1e303e0b9
Source dataset
uspto-grants-2011_12
Patent number
US08084476B2

Reaction notes

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