Carbon Dioxide → 6-Fluoro-2,4-dimethyl-nicotinic acid

HRID 1782558Notes

Reaction equation

HRID 1782558 reaction equation
Br[C:2]1[C:3]([CH3:10])=[N:4][C:5]([F:9])=[CH:6][C:7]=1[CH3:8].[Li]C(C)(C)C.[C:16](=[O:18])=[O:17]>CCOCC>[F:9][C:5]1[CH:6]=[C:7]([CH3:8])[C:2]([C:16]([OH:18])=[O:17])=[C:3]([CH3:10])[N:4]=1

Participants

5

Reactant 3

HCID 280Carbon DioxideHCID 689735143-Bromo-6-fluoro-2,4-dimethylpyridineHCID 178418306HCID 178418306, compound

Product 1

HCID 687753516-Fluoro-2,4-dimethyl-nicotinic acidYield 73%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-bromo-2,4-dimethyl-6-fluoropyridine (1.45 g, 7.10 mmol) in anhydrous Et2O (25 mL) at −78° C. was added t-BuLi (1.7M in pentane, 8.8 mL, 15 mmol) dropwise. After addition the mixture was stirred at −78° C. for 10 min, and CO2 was introduced. After 10 min the cooling bath was removed, and the bubbling of CO2 was continued until the mixture was warmed to 0° C. Water (30 mL) was then added and Et2O was removed. The aqueous layer was washed CH2Cl2 (2×30 mL) and acidified with 6N HCl, resulting in precipitation of a pale brown solid (0.87 g, 73%) which was collected by filtration and dried under vacuum. 1H NMR (CD3OD): δ 2.38 (s, 3H), 2.46 (s, 3H), 6.69 (s, 1H). 19F NMR (CD3OD): δ 0.63.

Workup

  1. additionAfter addition the mixture
  2. customAfter 10 min the cooling bath was removed
  3. customthe bubbling of CO2
  4. temperaturewas warmed to 0° C
  5. additionWater (30 mL) was then added
  6. customEt2O was removed
  7. washThe aqueous layer was washed CH2Cl2 (2×30 mL)

Sources & evidence

ORD record
ord-530c13a757684a41ba0314864b7f377d
Source dataset
uspto-grants-2009_03
Patent number
US07498346B2

Reaction notes

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