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

HRID 855220Notes

Reaction equation

HRID 855220 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](F)([F:26])[O:16][C:17]1[CH:18]=[C:19]([CH2:23][CH2:24][NH2:25])[CH:20]=[CH:21][CH:22]=1.C(=O)([O-])[O-].[K+].[K+].[BH4-].[Na+].Cl>CO>[C:1]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9][NH:25][CH2:24][CH2:23][C:19]2[CH:20]=[CH:21][CH:22]=[C:17]([O:16][CH:15]([F:14])[F:26])[CH:18]=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 574385032-[3-(Trifluoromethoxy)phenyl]ethan-1-amine hydrochloride

Product 1

HCID 68576819(4-Tert-butyl-benzyl)-[2-(3-difluoromethoxy-phenyl)-ethyl]-amineYield 89%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

0.55 ml of 4-tert-butylbenzaldehyde (9.19 mmol), 1.37 g of 2-(3-trifluoromethoxy-phenyl)-ethylamine hydrochloride (6.13 mmol) and 0.304 g of potassium carbonate (6.13 mmol) were suspended in 18 ml methanol at rt, and after stirring for 30 min at rt, were refluxed for 2.5 h. After cooling down to rt, 348 mg (9.19 mmol) of sodium borohydride were added and after stirring for 5 min at rt, the reaction mixture was refluxed for 22 h. After cooling down to rt, the reaction mixture was treated with 0.4 ml 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 to give 1.82 g off-white oil (89%). MS (ISP) 334.3 (M+H)+.

Workup

  1. temperaturewere refluxed for 2.5 h
  2. temperatureAfter cooling down to rt
  3. stirringafter stirring for 5 min at rt
  4. temperaturethe reaction mixture was refluxed for 22 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

Sources & evidence

ORD record
ord-ef7b0242438a4f9f91a856fe98ebf1ee
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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