Hydrochloric Acid → (4-Tert-butyl-benzyl)-[2-(4-fluoro-3-trifluoromethyl-phenyl)-ethyl]-amine

HRID 639524Notes

Reaction equation

HRID 639524 reaction equation
[C:1]([C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[F:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][NH2:23])=[CH:17][C:16]=1[C:24]([F:27])([F:26])[F:25].C(=O)([O-])[O-].[K+].[K+].[BH4-].[Na+].Cl>CO>[C:1]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9][NH:23][CH2:22][CH2:21][C:18]2[CH:19]=[CH:20][C:15]([F:14])=[C:16]([C:24]([F:27])([F:25])[F:26])[CH:17]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 703244-tert-ButylbenzaldehydeHCID 4311764Sodium borohydrideHCID 685582252-(4-Fluoro-3-trifluoromethyl-phenyl)-ethylamine hydrochloride

Product 1

HCID 68563599(4-Tert-butyl-benzyl)-[2-(4-fluoro-3-trifluoromethyl-phenyl)-ethyl]-amineYield 90.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 4-tert-butylbenzaldehyde (0.62 mL, 3.69 mmol), 2-(4-fluoro-3-trifluoromethyl-phenyl)-ethylamine hydrochloride (600 mg, 2.46 mmol), and potassium carbonate (340 mg, 2.46 mmol) in methanol (7 mL) was stirred for 30 min at RT and subsequently refluxed for 2 h. After cooling to RT, sodium borohydride (140 mg, 3.69 mmol) was added and reaction mixture was refluxed for 3 h. After cooling, the reaction mixture was treated with 1 M aq. hydrochloric acid solution (0.5 M) at RT and concentrated. The residue was partitioned between water and ethyl acetate. After separation of the organic phase, the aqueous phase was extracted with ethyl acetate and the combined organic phases were washed with brine, dried with magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography (SiO2; ethyl acetate/heptane 1:4 then 1:2) to afford the title compound (784 mg, 90%). Light yellow oil, MS (ISP) 354.3 (M+H)+.

Workup

  1. temperaturesubsequently refluxed for 2 h
  2. temperatureAfter cooling to RT
  3. customreaction mixture
  4. temperaturewas refluxed for 3 h
  5. temperatureAfter cooling
  6. concentrationconcentrated
  7. customThe residue was partitioned between water and ethyl acetate
  8. customAfter separation of the organic phase
  9. extractionthe aqueous phase was extracted with ethyl acetate
  10. washthe combined organic phases were washed with brine
  11. dry with materialdried with magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe residue was purified by column chromatography (SiO2

Sources & evidence

ORD record
ord-6f4480d9706143b094a9fa8afc3c38de
Source dataset
uspto-grants-2010_04
Patent number
US07691876B2

Reaction notes

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