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

HRID 855221Notes

Reaction equation

HRID 855221 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.[Cl:14][C:15]1[C:16]([F:24])=[C:17]([CH2:21][CH2:22][NH2:23])[CH:18]=[CH:19][CH:20]=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:23][CH2:22][CH2:21][C:17]2[CH:18]=[CH:19][CH:20]=[C:15]([Cl:14])[C:16]=2[F:24])=[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 687008102-(3-Chloro-2-fluorophenyl)ethan-1-amine hydrochloride

Product 1

HCID 69342716(4-Tert-butyl-benzyl)-[2-(3-chloro-2-fluoro-phenyl)-ethyl]-amineYield 56%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1.2 ml of 4-tert-butylbenzaldehyde (7.14 mmol), 1 g of 2-(3-chloro-2-fluoro-phenyl)-ethylamine hydrochloride (4.76 mmol) and 658 mg of potassium carbonate (4.76 mmol) were suspended in 14 ml methanol at rt, and after stirring for 30 min at rt, were refluxed for 2 h. After cooling down to rt, 270 mg (7.14 mmol) of sodium borohydride were added and after stirring for 5 min at rt, the reaction mixture was refluxed for 2.5 h. After cooling down to rt, the reaction mixture was treated with 1.2 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. The residue was purified by column chromatography (40 g silica gel; EtOAc/heptane 1:4) to give 860 mg light yellow oil (56%). MS (ISP) 320.3 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-e596c89183d140ac9046b65396618b44
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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