4-tert-Butylbenzaldehyde → (4-Tert-butyl-benzyl)-[2-(3,5-difluoro-phenyl)-ethyl]-amine

HRID 855193Notes

Reaction equation

HRID 855193 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].[F:13][C:14]1[CH:15]=[C:16]([CH2:21][CH2:22][NH2:23])[CH:17]=[C:18]([F:20])[CH:19]=1.[BH4-].[Na+]>CO.Cl>[C:1]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9][NH:23][CH2:22][CH2:21][C:16]2[CH:17]=[C:18]([F:20])[CH:19]=[C:14]([F:13])[CH:15]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 703244-tert-ButylbenzaldehydeHCID 36736652-(3,5-Difluorophenyl)ethan-1-amineHCID 4311764Sodium borohydride

Product 1

HCID 69342901(4-Tert-butyl-benzyl)-[2-(3,5-difluoro-phenyl)-ethyl]-amineYield 83%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 887MethanolSolvent

Procedure

0.67 ml of 4-tert-butylbenzaldehyde (3.87 mmol) and 500 mg 2-(3,5-difluoro-phenyl)-ethylamine (2.58 mmol) were dissolved in 7.5 ml methanol at rt, and after stirring for 30 min at rt, were refluxed for 4 h. After cooling down to rt, 147 mg (3.87 mmol) sodium borohydride were added and after stirring for 5 min at rt, the reaction mixture was then refluxed for 2.5 h. After cooling down to rt, the reaction mixture was treated with 10 drops 1 N HCl and concentrated in vacuo. The residue was diluted with water/EtOAc. After separation of the organic phase, the aqueous phase was extracted with EtOAc and the combined organic phases were washed with brine, dried with magnesium sulfate, filtered off and concentrated in vacuo. The residue was purified by column chromatography (40 g silica gel; EtOAc/heptane 1:2) to give 653 mg light yellow oil (83%). MS (ISP) 304.2 (M+H)+.

Workup

  1. temperaturewere refluxed for 4 h
  2. temperatureAfter cooling down to rt
  3. stirringafter stirring for 5 min at rt
  4. temperaturethe reaction mixture was then refluxed for 2.5 h
  5. temperatureAfter cooling down to rt
  6. concentrationconcentrated in vacuo
  7. additionThe residue was diluted with water/EtOAc
  8. customAfter separation of the organic phase
  9. extractionthe aqueous phase was extracted with EtOAc
  10. washthe combined organic phases were washed with brine
  11. dry with materialdried with magnesium sulfate
  12. filtrationfiltered off
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by column chromatography (40 g silica gel; EtOAc/heptane 1:2)

Sources & evidence

ORD record
ord-aeba69b61d11416eaa67d0ade6812079
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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