Dimethylformamide → Ethyl 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate

HRID 1081412Notes

Reaction equation

HRID 1081412 reaction equation
[Cl:1][C:2]1[N:11]=[C:10]2[C:5]([C:6](=[O:18])[C:7]([C:15]([OH:17])=[O:16])=[CH:8][N:9]2[CH:12]2[CH2:14][CH2:13]2)=[CH:4][C:3]=1[F:19].CN(C)C=O.[C:25](Cl)(=O)[C:26](Cl)=O>C(O)C.ClCCl>[CH2:25]([O:16][C:15]([C:7]1[C:6](=[O:18])[C:5]2[C:10](=[N:11][C:2]([Cl:1])=[C:3]([F:19])[CH:4]=2)[N:9]([CH:12]2[CH2:14][CH2:13]2)[CH:8]=1)=[O:17])[CH3:26]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chloride2×HCID 110551427-Chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid

Product 1

HCID 11722954Ethyl 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylateYield 50%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

7-Chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, (U.S. Pat. No. 4,663,457) (20.0 g, 71 mmol) and dimethylformamide (0.5 mL) were added to dichloromethane (750 mL) to give a tan slurry. Oxalyl chloride (7.4 mL, 85 mmol) was added to this slurry over one minute and the reaction mixture stirred for 90 minutes, then an additional 2.0 mL of oxalyl chloride was added and stirring continued for 60 minutes. To the resulting brown solution was added absolute ethanol (4.3 mL, 78 mmol) and the mixture stirred for 4 hours and then cooled to 0° C. and stored overnight. The reaction was warmed to room temperature and an additional 2 mL of absolute ethanol was added and the stirring continued for 3 hours. The reaction was evaporated to a brown solid. The solid was heated in THF, filtered, and cooled to 0° C. The crystals formed were collected and dried to give the title compound (11.1 g, 50%).

Workup

  1. customto give a tan slurry
  2. stirringstirring
  3. waitcontinued for 60 minutes
  4. stirringthe mixture stirred for 4 hours
  5. waitstored overnight
  6. temperatureThe reaction was warmed to room temperature
  7. waitthe stirring continued for 3 hours
  8. customThe reaction was evaporated to a brown solid
  9. temperatureThe solid was heated in THF
  10. filtrationfiltered
  11. temperaturecooled to 0° C
  12. customThe crystals formed
  13. customwere collected
  14. customdried

Sources & evidence

ORD record
ord-ed23b44cf04742c989a5eaa15baae7e1
Source dataset
uspto-grants-1996_12
Patent number
US05585491

Reaction notes

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