Cyclopropylamine → Fluoroquinolonic acid

HRID 47876Notes

Reaction equation

HRID 47876 reaction equation
C([O:3][C:4](=[O:21])[C:5](=[CH:17]OCC)[C:6](=[O:16])[C:7]1[CH:12]=[C:11]([F:13])[C:10]([Cl:14])=[CH:9][C:8]=1Cl)C.[CH:22]1([NH2:25])[CH2:24][CH2:23]1>C(Cl)Cl>[Cl:14][C:10]1[CH:9]=[C:8]2[C:7]([C:6](=[O:16])[C:5]([C:4]([OH:3])=[O:21])=[CH:17][N:25]2[CH:22]2[CH2:24][CH2:23]2)=[CH:12][C:11]=1[F:13]

Participants

4

Reactant 2

HCID 69828CyclopropylamineHCID 53427585Ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-ethoxyacrylate

Product 1

HCID 483180Fluoroquinolonic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4 (80 g) in methylene chloride (800 mL), cyclopropylamine (44.0 g) was added with cooling below 10° C. The mixture was stirred at room temperature for 1 h and evaporated to a dry mixture. To the dry mixture in dimethoxyethane (800 mL), a 60% sodium hydride-in-oil suspension (12.0 g) was added slowly with cooling and stirring. The mixture was heated at 80-85° C. for 3 h under nitrogen atmosphere. It was cooled and water (5 L) was added and the precipitate was filtered and washed with water and dried. The ester was suspended in tetrahydrofuran (800 mL). A solution of sodium hydroxide (20.0 g) in water (500 mL) was added and the mixture was refluxed for 2 h. It was cooled and acidified with acetic acid and the precipitate was filtered. The solid was washed with water and acetone. wt=19.0 g of (7). m.p.=235-240° C.

Workup

  1. temperaturewith cooling below 10° C
  2. customevaporated to a dry mixture
  3. additionTo the dry mixture in dimethoxyethane (800 mL), a 60% sodium hydride-in-oil suspension (12.0 g) was added slowly
  4. temperaturewith cooling
  5. stirringstirring
  6. temperatureThe mixture was heated at 80-85° C. for 3 h under nitrogen atmosphere
  7. temperatureIt was cooled
  8. additionwater (5 L) was added
  9. filtrationthe precipitate was filtered
  10. washwashed with water
  11. customdried
  12. additionA solution of sodium hydroxide (20.0 g) in water (500 mL) was added
  13. temperaturethe mixture was refluxed for 2 h
  14. temperatureIt was cooled
  15. filtrationthe precipitate was filtered
  16. washThe solid was washed with water and acetone

Sources & evidence

ORD record
ord-7b128a3d112f49cfae0b3517a46e1728
Source dataset
uspto-grants-2004_03
Patent number
US06699989B1

Reaction notes

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