Water → N-{1-[2-(aminomethyl)-4-chlorophenyl]-2,2-difluoroethyl}-N-(4-methoxyphenyl)amine

HRID 1058234Notes

Reaction equation

HRID 1058234 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:20]([CH2:23][C:24]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=1[CH:31]([NH:35][C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=1)[CH:32]([F:34])[F:33])=[N+]=[N-].O>C1COCC1>[NH2:20][CH2:23][C:24]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=1[CH:31]([NH:35][C:36]1[CH:37]=[CH:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=1)[CH:32]([F:34])[F:33]

Participants

5

Reactant 3

HCID 962WaterHCID 11776TriphenylphosphineHCID 18672408HCID 18672408, compound

Product 1

HCID 18672348N-{1-[2-(aminomethyl)-4-chlorophenyl]-2,2-difluoroethyl}-N-(4-methoxyphenyl)amineYield 73.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triphenylphosphine (0.344 g, 1.31 mmol) was added to a stirred solution of N-{1-[2-(azidomethyl)-4-chlorophenyl]-2,2-difluoroethyl}-N-(4-methoxyphenyl)amine (0.463 g, 1.31 mmol) and water (0.02 mL, 1.31 mmol) in THF (2.6 mL). The solution was stirred at ambient temperature for 2 h and the solvent was removed under reduced pressure. The residue was dissolved in MeOH (5 mL). One KOH pellet was added and the mixture was refluxed for 5 min. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc and 1M HCl. The aqueous layer was basicified with 1M NaOH and the solution was extracted with diethyl ether. The organic phase was dried (Na2SO4) and reduced in vacuo and the residue was purified by column chromatography on silica (eluting with ammonium hydroxide/methanol/chloroform, 1:9:90) to give N-{1-[2-(aminomethyl)-4-chlorophenyl]-2,2-difluoroethyl}-N-(4-methoxyphenyl)amine (0.314 g) as an oil: MS 327.5 (M+1).

Workup

  1. customthe solvent was removed under reduced pressure
  2. dissolutionThe residue was dissolved in MeOH (5 mL)
  3. additionOne KOH pellet was added
  4. temperaturethe mixture was refluxed for 5 min
  5. customThe solvent was removed under reduced pressure
  6. customthe residue was partitioned between EtOAc and 1M HCl
  7. extractionthe solution was extracted with diethyl ether
  8. dry with materialThe organic phase was dried (Na2SO4)
  9. customthe residue was purified by column chromatography on silica (eluting with ammonium hydroxide/methanol/chloroform, 1:9:90)

Sources & evidence

ORD record
ord-66eec3d91121446d83f0f405f8df9f1e
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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