Phosphoric Acid → 9-fluoro-8-chloro-5-methyl-6,7-dihydro-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acid

HRID 1649433Notes

Reaction equation

HRID 1649433 reaction equation
[F:1][C:2]1[C:3]([Cl:13])=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]([CH3:12])[CH2:6][CH2:5]2.C([O:16][CH:17]=[C:18]([C:24](OCC)=O)[C:19]([O:21]CC)=[O:20])C.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.P(=O)(O)(O)O.[OH-].[Na+]>>[F:1][C:2]1[CH:11]=[C:10]2[C:9]3[N:8]([CH:24]=[C:18]([C:19]([OH:21])=[O:20])[C:17]2=[O:16])[CH:7]([CH3:12])[CH2:6][CH2:5][C:4]=3[C:3]=1[Cl:13]

Participants

6

Reactant 5

HCID 1004Phosphoric AcidHCID 6871Diethyl (ethoxymethylene)malonateHCID 14798Sodium HydroxideHCID 14812Phosphorus oxide (P4O10)HCID 155717755-Chloro-6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline

Product 1

HCID 134729989-fluoro-8-chloro-5-methyl-6,7-dihydro-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acidYield 54%

Conditions

Temperature
160 °C

Procedure

A mixture of 1.5 g of 6-fluoro-5-chloro-1,2,3,4-tetrahydroquinaldine and 1.8 g of diethyl ethoxymethylenemalonate was heated at 160° C. for 30 minutes. Then, 14 g of polyphosphoric acid prepared from 7 g of phosphorus pentoxide and 7 g of phosphoric acid was added to the mixture and the resulting mixture was allowed to react by heating at 140° to 150° C. for 1 hour. After completion of the reaction, the reaction mixture was poured onto 100 g of ice, followed by adjusting the mixture to pH 6 to 7 with a 10 N aqueous sodium hydroxide solution. The precipitates were collected by filtration and added to 30 ml of concentrated hydrochloric acid followed by heating under reflux. After completion of the reaction 50 ml of water was added to the reaction mixture to precipitate crystals. The crystals thus-obtained were collected by filtration, washed with water and dried. Recrystallization of the crude crystals from ethanol gave 1.2 g of 9-fluoro-8-chloro-5-methyl-6,7-dihydro-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acid as white rhombic crystals having a melting point of 297° to 298° C.

Workup

  1. additionwas added to the mixture
  2. customto react
  3. temperatureby heating at 140° to 150° C. for 1 hour
  4. customAfter completion of the reaction
  5. filtrationThe precipitates were collected by filtration
  6. additionadded to 30 ml of concentrated hydrochloric acid
  7. temperatureby heating
  8. temperatureunder reflux
  9. customAfter completion of the reaction 50 ml of water
  10. additionwas added to the reaction mixture
  11. customto precipitate crystals
  12. customThe crystals thus-obtained
  13. filtrationwere collected by filtration
  14. washwashed with water
  15. customdried
  16. customRecrystallization of the crude crystals from ethanol

Sources & evidence

ORD record
ord-53a7565925234c17bf0a6031a3ba6c99
Source dataset
uspto-grants-1983_11
Patent number
US04416884

Reaction notes

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