Hydrochloric Acid → 3-{[1-(3,4-Difluorophenyl)ethylamino]-(3-methoxyphenyl)methyl}-4-methoxyphenylamine

HRID 2269439Notes

Reaction equation

HRID 2269439 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]([NH:11][CH:12]([C:21]2[CH:26]=[C:25]([N+:27]([O-])=O)[CH:24]=[CH:23][C:22]=2[O:30][CH3:31])[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=2)[CH3:10])[CH:5]=[CH:6][C:7]=1[F:8].[Sn](Cl)Cl.Cl.[OH-].[Na+]>C(O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:9]([NH:11][CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=2)[C:21]2[CH:26]=[C:25]([NH2:27])[CH:24]=[CH:23][C:22]=2[O:30][CH3:31])[CH3:10])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24479Stannous ChlorideHCID 18334104N-[1-(3,4-Difluorophenyl)ethyl]-N-[(2-methoxy-5-nitrophenyl)-(3-methoxyphenyl)methyl]amine

Product 1

HCID 183470643-{[1-(3,4-Difluorophenyl)ethylamino]-(3-methoxyphenyl)methyl}-4-methoxyphenylamine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

810 mg of N-[1-(3,4-difluorophenyl)ethyl]-N-[(2-methoxy-5-nitrophenyl)-(3-methoxyphenyl)methyl]amine [prepared as described in step (a) above] and 1.43 g of tin (II) chloride were added to 20 ml of a 1:1 by volume mixture of concentrated hydrochloric acid and ethanol, and then the mixture was heated under reflux for 2 hours. The reaction mixture was adjusted to a weakly alkaline pH by the addition of excess sodium hydroxide, after which it was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and then distilled under reduced pressure to remove the solvent. The residue was separated and purified by reverse phase HPLC [acetonitrile: acetate buffer (water:acetic acid:triethylamine=1000:2:2)=50:50], to obtain 235 mg of isomer A of the title compound as a yellow oil. The isomer mixture was purified further by chromatography through a silica gel column using a 1:1 by volume mixture of cyclohexane and ethyl acetate as the eluant, to obtain 187 mg of isomer B as a yellow oil.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 2 hours
  3. extractionafter which it was extracted with ethyl acetate
  4. washThe extract was washed with a saturated aqueous solution of sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. distillationdistilled under reduced pressure
  7. customto remove the solvent
  8. customThe residue was separated
  9. custompurified by reverse phase HPLC [acetonitrile: acetate buffer (water:acetic acid:triethylamine=1000:2:2)=50:50]

Sources & evidence

ORD record
ord-6d48b9b213504ec2ba7e71e1f807c2c0
Source dataset
uspto-grants-2001_12
Patent number
US06329405B1

Reaction notes

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