3-Chloro-4-methoxyaniline → HCID 86738118, compound

HRID 1155523Notes

Reaction equation

HRID 1155523 reaction equation
[Na].[CH3:2][O:3][C:4](=[S:9])[C:5]([CH3:8])=[CH:6]O.[Cl:10][C:11]1[CH:12]=[C:13]([CH:15]=[CH:16][C:17]=1[O:18][CH3:19])[NH2:14]>CO.O.Cl>[Cl:10][C:11]1[CH:12]=[C:13]([CH:15]=[CH:16][C:17]=1[O:18][CH3:19])[NH:14][CH:6]=[C:5]([CH3:8])[C:4]([O:3][CH3:2])=[S:9]

Participants

7

Reactant 3

HCID 214413-Chloro-4-methoxyanilineHCID 5360545Sodium2×HCID 136359194HCID 136359194, compound

Product 1

HCID 86738118HCID 86738118, compound

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Sodium (7.65 g.) was dissolved in anhydrous methanol (450 ml.) and the solution evaporated to dryness. The resulting sodium methoxide was suspended in anhydrous diethyl ether (300 ml.). The suspension was stirred at 0° and methyl methylthioacetate (40 g.) was added dropwise. The mixture was stirred at 0° for 1 hour and then treated dropwise with methyl formate (21 g.). The mixture was stirred at 0° for 1 hour and then stirred overnight at room temperature. The resulting suspension of solid was extracted with water (300 ml.) and the aqueous extract adjusted to 333 ml. with water. This aqueous extract containing methyl-3-hydroxy-2-methylthioacrylate, sodium salt (0.33 mole) was added to a stirred solution of 3-chloro-4-methoxyaniline (52 g.) in a mixture of water (800 ml.) and 11.6 N hydrochloric acid (33 ml.) at 0°. The mixture was stirred for 30 minutes and the product collected by filtration to give the novel intermediate compound methyl 3-(3-chloro-4-methoxyanilino)-2-methylthioacrylate, m.p. 110°-112°. This acrylate (77.6 g.) was added to diphenyl ether (200 ml.) stirred at 250° under nitrogen. After stirring at 250° for 15 minutes the mixture was cooled. The resulting precipitate was collected by filtration to give the novel intermediate compound 7-chloro-6-methoxy-3-methylthio-4-quinolone, m.p. 288°-290° (dec.) Examination by thin layer chromatography showed the presence of a minor amount of the corresponding 5-chloro isomer.

Workup

  1. customthe solution evaporated to dryness
  2. additionmethyl methylthioacetate (40 g.) was added dropwise
  3. stirringThe mixture was stirred at 0° for 1 hour
  4. additiontreated dropwise with methyl formate (21 g.)
  5. stirringThe mixture was stirred at 0° for 1 hour
  6. stirringstirred overnight at room temperature
  7. additionThe resulting suspension of solid
  8. extractionwas extracted with water (300 ml.)
  9. extractionthe aqueous extract
  10. extractionThis aqueous extract
  11. stirringThe mixture was stirred for 30 minutes
  12. filtrationthe product collected by filtration

Sources & evidence

ORD record
ord-f9b915cc4447404fa72ee80f0bb4380e
Source dataset
uspto-grants-1981_11
Patent number
US04302460

Reaction notes

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