Cyclopropylamine → 1-Cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic Acid Ethyl Ester

HRID 1681197Notes

Reaction equation

HRID 1681197 reaction equation
F[C:2]1[C:15]([F:16])=[C:14]([F:17])[C:13]([F:18])=[CH:12][C:3]=1[C:4]([CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])=[O:5].CO[CH:21](OC)[N:22]([CH3:24])C.[CH:27]1(N)C[CH2:28]1>O1CCCC1>[CH:21]1([N:22]2[C:2]3[C:3](=[CH:12][C:13]([F:18])=[C:14]([F:17])[C:15]=3[F:16])[C:4](=[O:5])[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:24]2)[CH2:28][CH2:27]1

Participants

5

Reactant 3

HCID 69828CyclopropylamineHCID 78373Dimethylformamide dimethyl acetalHCID 600916Ethyl 3-oxo-(2,3,4,5-tetrafluorophenyl)propanoate

Product 1

HCID 5354151-Cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic Acid Ethyl EsterYield 86.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
108 °C

Procedure

A 12 L stirred flask was charged with 4.8 L of tetrahydrofuran, 1584 g of ethyl 2,3,4,5-tetrafluorobenzoylacetate and 834 ml of dimethylformamide dimethyl acetal. After establishing a nitrogen atmosphere, this mixture was heated to reflux for 1 hour and then stirred at ambient temperature for four hours. The mixture was cooled and maintained at 4°-5° C. while adding 438 ml of cyclopropylamine over a period of 35 minutes. It was then stirred at 3°-5° C. for 1 hour and concentrated in vacuo. The yellow crystalline solid was dissolved in 3.6 L of dimethylformamide and 912 g of powdered potassium carbonate was added with strong stirring. The slurry was then heated on a steam bath for 1 hour (maximum internal temperature was 108° C. for 5 minutes). The hot mixture was poured into 30 L of cold water. Filtration, washing first with 6 L of cold water and then 6 L of cold ethanol followed by drying in vacuo at 50° C. gave 1615 g of product (86.5% yield).

Workup

  1. temperaturethis mixture was heated
  2. temperatureto reflux for 1 hour
  3. stirringstirred at ambient temperature for four hours
  4. temperatureThe mixture was cooled
  5. temperaturemaintained at 4°-5° C.
  6. stirringIt was then stirred at 3°-5° C. for 1 hour
  7. concentrationconcentrated in vacuo
  8. dissolutionThe yellow crystalline solid was dissolved in 3.6 L of dimethylformamide
  9. addition912 g of powdered potassium carbonate was added with strong stirring
  10. additionThe hot mixture was poured into 30 L of cold water
  11. filtrationFiltration
  12. washwashing first with 6 L of cold water
  13. customby drying in vacuo at 50° C.

Sources & evidence

ORD record
ord-b2181f895f604cbf927cb45db3484aac
Source dataset
uspto-grants-1992_12
Patent number
US05169853

Reaction notes

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