Hydrochloric Acid → 4-{[1-(5-Chloro-3-methyl-1-benzofuran-2-yl)-3-methylbutyl]amino}benzoic acid

HRID 2091164Notes

Reaction equation

HRID 2091164 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([CH:10](Cl)[CH2:11][CH:12]([CH3:14])[CH3:13])=[C:7]([CH3:16])[C:6]=2[CH:17]=1.[NH2:18][C:19]1[CH:28]=[CH:27][C:22]([C:23]([O:25]C)=[O:24])=[CH:21][CH:20]=1.[I-].[Na+].C(=O)([O-])[O-].[Na+].[Na+].Cl.[OH-].[Na+]>C(O)C.O1CCCC1.CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([CH:10]([NH:18][C:19]3[CH:28]=[CH:27][C:22]([C:23]([OH:25])=[O:24])=[CH:21][CH:20]=3)[CH2:11][CH:12]([CH3:14])[CH3:13])=[C:7]([CH3:16])[C:6]=2[CH:17]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 12082Methyl 4-aminobenzoateHCID 14798Sodium HydroxideHCID 667784465-Chloro-2-(1-chloro-3-methylbutyl)-3-methyl-1-benzofuran

Product 1

HCID 667771684-{[1-(5-Chloro-3-methyl-1-benzofuran-2-yl)-3-methylbutyl]amino}benzoic acidYield 43%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 5-chloro-2-(1-chloro-3-methylbutyl)-3-methyl-1-benzofuran (668 mg) synthesized above, methyl 4-aminobenzoate (410 mg), sodium iodide (737 mg) and N,N-dimethylformamide (10 mL) was added sodium carbonate (521 mg) and the mixture was stirred at 80° C. for 8 hr. 1N Hydrochloric acid was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (15% ethyl acetate/hexane) to give a yellow oil. To a mixture of the obtained oil, tetrahydrofuran (10 mL) and ethanol (10 mL) was added 1N aqueous sodium hydroxide solution (10.0 mL), and the mixture was stirred with heating under reflux for 8 hr, and concentrated under reduced pressure. The residue was dissolved in water (20 mL), and 1N hydrochloric acid (10.0 mL) was added at 0° C. The resulting precipitate was collected by filtration to give the title object compound (394 mg, 43%) as a pale-yellow solid.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (15% ethyl acetate/hexane)
  8. customto give a yellow oil
  9. stirringthe mixture was stirred
  10. temperaturewith heating
  11. temperatureunder reflux for 8 hr
  12. concentrationconcentrated under reduced pressure
  13. dissolutionThe residue was dissolved in water (20 mL)
  14. addition1N hydrochloric acid (10.0 mL) was added at 0° C
  15. filtrationThe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-f433c0ac6882438fa126f05a1f51f76e
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

Loading…