Lithium iodide → 2-Chloro-4-cyano-6-fluorobenzoic acid

HRID 449928Notes

Reaction equation

HRID 449928 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]([C:12]#[N:13])[CH:9]=[C:8]([F:14])[C:3]=1[C:4]([O:6]C)=[O:5].[I-].[Li+]>N1C=CC=CC=1>[Cl:1][C:2]1[CH:11]=[C:10]([C:12]#[N:13])[CH:9]=[C:8]([F:14])[C:3]=1[C:4]([OH:6])=[O:5]

Participants

4

Reactant 2

HCID 66321Lithium iodideHCID 67128641HCID 67128641, compound

Product 1

HCID 668014122-Chloro-4-cyano-6-fluorobenzoic acidYield 89%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
115 °C

Procedure

To a solution of methyl 2-chloro-4-cyano-6-fluorobenzoate (1.953 g, 9.143 mmoles) in pyridine (50 mL) was added lithium iodide (2.45 g, 18.3 mmoles). The reaction mixture was heated at 115° C. for 3 hours. The reaction was concentrated under reduced pressure and the resulting solid was triturated with EtOAc. The solid was dissolved in water and acidified to pH 4 with 1 N HCl. The aqueous solution was extracted with EtOAc (3×30 mL). The combined organic extracts were dried with Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel chromatography [0-20% (10% formic acid in MeOH)/DCM] to afford 2-chloro-4-cyano-6-fluorobenzoic acid as a white solid (1.616 g, yield: 89%). 1H NMR (400 MHz, CDCl3) δ 7.58 (s, 1H), 7.40 (dd, J=8.1, 1.0 Hz, 1H). LCMS (APCI+) [M+H]+ 200.0.

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. customthe resulting solid was triturated with EtOAc
  3. dissolutionThe solid was dissolved in water
  4. extractionThe aqueous solution was extracted with EtOAc (3×30 mL)
  5. dry with materialThe combined organic extracts were dried with Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography [0-20% (10% formic acid in MeOH)/DCM]

Sources & evidence

ORD record
ord-24f42be8f5c0451b863571bd52baaae1
Source dataset
uspto-grants-2013_07
Patent number
US08486950B2

Reaction notes

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