Methyl vinyl ketone → 5-(3,4-Dichlorophenoxy)-6-methoxy-4-methyl-8-nitroquinoline

HRID 842761Notes

Reaction equation

HRID 842761 reaction equation
Cl.[N+:2]([C:5]1[CH:11]=[C:10]([O:12][CH3:13])[C:9]([O:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=2)=[CH:8][C:6]=1[NH2:7])([O-:4])=[O:3].[CH:23]([C:25]([CH3:27])=O)=[CH2:24]>P(=O)(O)(O)O>[Cl:22][C:17]1[CH:16]=[C:15]([CH:20]=[CH:19][C:18]=1[Cl:21])[O:14][C:9]1[C:10]([O:12][CH3:13])=[CH:11][C:5]([N+:2]([O-:4])=[O:3])=[C:6]2[C:8]=1[C:25]([CH3:27])=[CH:23][CH:24]=[N:7]2

Participants

4

Reactant 2

HCID 6570Methyl vinyl ketone2×HCID 226159192-Nitro-4-methoxy-5-(3,4-dichlorophenoxy)aniline hydrochloride

Product 1

HCID 6332425-(3,4-Dichlorophenoxy)-6-methoxy-4-methyl-8-nitroquinolineYield 9.6%

Reagents, catalysts & solvents 1

HCID 1004Phosphoric AcidSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of 83 g of 2-nitro-4-methoxy-5-(3,4-dichlorophenoxy)aniline hydrochloride (0.22 mole) polyphosphoric acid in 250 ml of 85% phosphoric acid was heated in a nitrogen atmosphere at 110-120° C. and 32.17 g of methyl vinyl ketone (0.46 mole) was added dropwise under vigorous stirring. After the addition was complete, the mixture was stirred and maintained at 110-120° C. for a further 4 hours. An additional 14 g of methyl vinyl ketone (0.2 mole) was added and the mixture was heated for a further 4 hours. The reaction mixture was poured into ice cold sodium hydroxide solution (pH 10-12) and left over night. The resulting precipitate was separated by filtration and dried. The solid was dissolved in chloroform and mixed with activated charcoal and filtered through a celite bed. The celite bed was washed with chloroform and the filtrate was concentrated to 400 ml under vacuum and diluted with methanol until a turbidity appeared and left overnight. The crystalline product formed was separated by decantation and crystallized from chloroform to give 8 g of pure product, 5-(3,4-dichlorophenoxy)-6-methoxy-4-methyl-8-nitroquinoline. The combined filtrates were evaporated to dryness and the residue was chromatographed over silica gel with 30% chloroform in hexane to yield a fraction from which the product which was crystallized (chloroform/methanol) to give 13 g of product.

Workup

  1. additionAfter the addition
  2. temperaturemaintained at 110-120° C. for a further 4 hours
  3. temperaturethe mixture was heated for a further 4 hours
  4. waitleft over night
  5. customThe resulting precipitate was separated by filtration
  6. customdried
  7. dissolutionThe solid was dissolved in chloroform
  8. additionmixed with activated charcoal
  9. filtrationfiltered through a celite bed
  10. washThe celite bed was washed with chloroform
  11. concentrationthe filtrate was concentrated to 400 ml under vacuum
  12. additiondiluted with methanol until a turbidity
  13. customThe crystalline product formed
  14. customwas separated by decantation
  15. customcrystallized from chloroform

Sources & evidence

ORD record
ord-4847d973d9f2473382c7e2ccb2a88375
Source dataset
uspto-grants-2002_04
Patent number
US06376511B2

Reaction notes

Loading…