Phosphoric Acid → 4-Methyl-5-fluoro-6-methoxy-8-nitroquinoline

HRID 1388565Notes

Reaction equation

HRID 1388565 reaction equation
[NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([O:11][CH3:12])=[C:4]([F:13])[CH:3]=1.O=[As](O[As](=O)=O)=O.P(=O)(O)(O)O.[CH:26]([C:28]([CH3:30])=O)=[CH2:27]>[OH-].[NH4+]>[CH3:30][C:28]1[C:3]2[C:2](=[C:7]([N+:8]([O-:10])=[O:9])[CH:6]=[C:5]([O:11][CH3:12])[C:4]=2[F:13])[N:1]=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 1004Phosphoric AcidHCID 6570Methyl vinyl ketoneHCID 14771Arsenic pentoxideHCID 2196205-Fluoro-4-methoxy-2-nitroaniline

Product 1

HCID 126110024-Methyl-5-fluoro-6-methoxy-8-nitroquinolineYield 58.3%

Reagents, catalysts & solvents 1

HCID 14923Ammonium HydroxideSolvent

Procedure

To a hot (92°), stirred mixture of 54.4 g (0.292 mol) of 4-amino-2-fluoro-5-nitroanisole (XIII), 50.2 g (0.218 mol) of arsenic pentoxide, and 300 mL of 88% phosphoric acid was added 24.5 g (0.349 mol) of methyl vinyl ketone, during 0.5 hour. The reaction mixture was heated at 95° for 2.5 hours, cooled, diluted with 2.0 L of ice-water, then basified with 700 mL of concentrated ammonium hydroxide. The solid which separated was collected on a filter, washed with water (4×1.0 L), then air dried; yield, 140.6 g. The material was extracted with chloroform (2.0 L). The extract was concentrated to 500 mL then chromatographed on a column of silica gel (900 g) using chloroform as the eluent. The fractions containing product were combined then concentrated in vacuo to a solid; yield, 21.8 g (31.6%). The product was suitable for further transformation. Additional material (40.2 g) was obtained from a similar run and a scouting run.

Workup

  1. temperatureThe reaction mixture was heated at 95° for 2.5 hours
  2. temperaturecooled
  3. customThe solid which separated
  4. customwas collected on a filter
  5. washwashed with water (4×1.0 L)
  6. customair dried
  7. customyield
  8. extractionThe material was extracted with chloroform (2.0 L)
  9. concentrationThe extract was concentrated to 500 mL
  10. customthen chromatographed on a column of silica gel (900 g)
  11. additionThe fractions containing product
  12. concentrationwere combined then concentrated in vacuo to a solid
  13. customyield

Sources & evidence

ORD record
ord-49358465756045ad8a4e96ce16213228
Source dataset
uspto-grants-1984_02
Patent number
US04431807

Reaction notes

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