Sulfuric Acid → Ethyl 3-(2,7-dichloro-6-fluoro-3-quinolyl)-3-oxopropionate

HRID 344848Notes

Reaction equation

HRID 344848 reaction equation
[Cl:1][C:2]1[C:11]([C:12]([OH:14])=O)=[CH:10][C:9]2[C:4](=[CH:5][C:6]([Cl:16])=[C:7]([F:15])[CH:8]=2)[N:3]=1.[Mg].S(=O)(=O)(O)[OH:19].[O:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1>ClC(Cl)Cl.S(Cl)(Cl)=O>[Cl:1][C:2]1[C:11]([C:12](=[O:14])[CH2:25][C:24]([O:23][CH2:27][CH3:26])=[O:19])=[CH:10][C:9]2[C:4](=[CH:5][C:6]([Cl:16])=[C:7]([F:15])[CH:8]=2)[N:3]=1

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 8028Tetrahydrofuran2×HCID 5462224MagnesiumHCID 147266242,7-Dichloro-6-fluoroquinoline-3-carboxylic acid

Product 1

HCID 14726625Ethyl 3-(2,7-dichloro-6-fluoro-3-quinolyl)-3-oxopropionate

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of 2,7-dichloro-6-fluoro-3-quinolinecarboxylic acid (38.75 g) in trichloromethane (410 cc) and thionyl chloride (24 cc) is heated to a temperature in the region of 60° C. with stirring for 6 hours. The solution obtained is concentrated to dryness under reduced pressure (20 kPa) at 50° C. The dry extract is taken up twice with toluene (200 cc in total) and concentrated again under reduced pressure under the same conditions as above. The yellow solid obtained (m.p. 124° C.), is dissolved in anhydrous tetrahydrofuran (230 cc). The solution obtained is introduced dropwise, with stirring, in the course of 30 minutes and at between 5° and 10° C. into a solution (200 cc) of magnesium chelate in tetrahydrofuran. The temperature is allowed to rise to 20° C. and the mixture is stirred for 1 and a half hours at this temperature. The solution obtained is introduced dropwise, with stirring and at a temperature in the region of 5° C. into 0.5 N sulphuric acid (1 liter). The temperature of the suspension obtained is allowed to rise to 20° C. and the mixture is stirred for a further 2 hours at this temperature. The product is extracted with ethyl acetate (1 liter), the organic and aqueous phases are filtered through diatomaceous silica for filtration which enables some slight insoluble matter to be removed and the aqueous phase is extracted twice more with ethyl acetate (500 cc). The combined organic extracts are washed with water (2×500 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (20 kPa) at 40° C. The residue is taken up with isopropyl ether (100 cc) at 20° C., drained and washed with isopropyl ether (2×30 cc). Ethyl 3-(2,7-dichloro-6-fluoro-3-quinolyl)-3-oxopropionate (40.55 g) is obtained in the form of a beige solid, m.p. 112°-114° C. This product is used without further purification for the subsequent steps.

Workup

  1. customThe solution obtained
  2. concentrationis concentrated to dryness under reduced pressure (20 kPa) at 50° C
  3. extractionThe dry extract
  4. concentrationconcentrated again under reduced pressure under the same conditions as above
  5. customThe yellow solid obtained (m.p. 124° C.)
  6. customThe solution obtained
  7. additionis introduced dropwise
  8. customto rise to 20° C.
  9. stirringthe mixture is stirred for 1 and a half hours at this temperature
  10. customThe solution obtained
  11. additionis introduced dropwise
  12. customThe temperature of the suspension obtained
  13. customto rise to 20° C.
  14. stirringthe mixture is stirred for a further 2 hours at this temperature
  15. extractionThe product is extracted with ethyl acetate (1 liter)
  16. filtrationthe organic and aqueous phases are filtered through diatomaceous silica for filtration which
  17. customto be removed
  18. extractionthe aqueous phase is extracted twice more with ethyl acetate (500 cc)
  19. washThe combined organic extracts are washed with water (2×500 cc)
  20. dry with materialdried over magnesium sulphate
  21. filtrationfiltered
  22. concentrationconcentrated to dryness under reduced pressure (20 kPa) at 40° C
  23. customis taken up with isopropyl ether (100 cc) at 20° C.
  24. washwashed with isopropyl ether (2×30 cc)

Sources & evidence

ORD record
ord-25c2247fb5c543fba82aad60d2fa44f9
Source dataset
uspto-grants-1991_10
Patent number
US05053509

Reaction notes

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