Thionyl Chloride → Ethyl 4-chloro-6-fluoroquinoline-3-carboxylate

HRID 1944549Notes

Reaction equation

HRID 1944549 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:15](=O)[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([F:17])[CH:13]=2)[NH:8][CH:7]=1)=[O:5])[CH3:2].S(Cl)([Cl:20])=O>>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[Cl:20])=[CH:13][C:12]([F:17])=[CH:11][CH:10]=2)=[O:5])[CH3:2]

Participants

3

Reactant 2

HCID 24386Thionyl ChlorideHCID 710779Ethyl 6-fluoro-4-hydroxyquinoline-3-carboxylate

Product 1

HCID 1479088Ethyl 4-chloro-6-fluoroquinoline-3-carboxylate

Procedure

A mixture of 6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl ester (4.4 g, 18.7 mmol) in thionyl chloride (50 mL) was heated at reflux for 3 hours (at 30 min. mixture changed to a clear solution). The resultant solution was cooled to room temperature, and the excess thionyl chloride was evaporated in vacuo. The residue was added to ammonium hydroxide on ice (note: highly exothermic). Let resultant mixture stir for 15 minutes, and the product was collected by filtration and washed generously with water. The solid was purified by flash chromatography, on silica gel, eluted with a gradient of ethyl acetate (0% to 30%) in heptane, to give the product, 4.24 g (89%) as a colorless solid. MS: m/z 253.8 (MH+).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 hours (at 30 min. mixture
  3. customthe excess thionyl chloride was evaporated in vacuo
  4. additionThe residue was added to ammonium hydroxide on ice (note
  5. filtrationthe product was collected by filtration
  6. washwashed generously with water
  7. customThe solid was purified by flash chromatography, on silica gel
  8. washeluted with a gradient of ethyl acetate (0% to 30%) in heptane
  9. customto give the product, 4.24 g (89%) as a colorless solid

Sources & evidence

ORD record
ord-ebf7b38d04be4b9488657b1271eb71f2
Source dataset
uspto-grants-2013_03
Patent number
US08394828B2

Reaction notes

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