Potassium Fluoride → 2-Fluoroquinoline-4-carboxylic acid methyl ester

HRID 47427

Reaction equation

HRID 47427 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]=[C:7](Cl)[CH:6]=1)=[O:4].[F-:16].[K+]>CS(C)(=O)=O.ClCCl.O>[CH3:1][O:2][C:3]([C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]=[C:7]([F:16])[CH:6]=1)=[O:4]

Participants

5

Reactant 2

HCID 522689Potassium FluorideHCID 5202936Methyl 2-chloroquinoline-4-carboxylate

Product 1

HCID 539678632-Fluoroquinoline-4-carboxylic acid methyl esterYield 66.3%

Reagents, catalysts & solvents 2

HCID 6213Dimethyl SulfoneSolventHCID 21908982Water methylene chlorideSolvent

Conditions

Temperature
180 °C

Procedure

2-Chloroquinoline-4-carboxylic acid methyl ester (1.14 g) in dimethylsulfone (4.0 g) was treated with potassium fluoride (2.5 g) and heated at 180° C. for 1 h. The reaction mixture was cooled to room temperature, diluted with dichloromethane:water (1:1, 200 ml), the organic phase separated, solvent removed at reduced pressure and the residue column chromatographed (silica gel, dichloromethane eluant) to give 2-fluoroquinoline-4-carboxylic acid methyl ester (0.7 g). 1H NMR (CDCl3) δ: 3.99 (3H, s), 7.57 (2H, m), 7.72 (1H, m), 7.95 (1H, d, J=8.5 Hz), 8.67 (1H, d, J=8.4 Hz). m/z (API+): 205 (MH+).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customthe organic phase separated
  3. customsolvent removed at reduced pressure
  4. customthe residue column chromatographed (silica gel, dichloromethane eluant)

Sources & evidence

ORD record
ord-c5db79bf0d3148d9bbb0dabc02bceb6e
Source dataset
uspto-grants-2004_03
Patent number
US06699879B1

Linked notes

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