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

HRID 855252Notes

Reaction equation

HRID 855252 reaction equation
[C:1]([C:5]1[CH:22]=[CH:21][C:8]([C:9]([NH:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=O)=[C:7]([Cl:23])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[OH-].[Na+]>C1COCC1>[C:1]([C:5]1[CH:22]=[CH:21][C:8]([CH2:9][NH:11][CH2:12][CH2:13][C:14]2[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=2)=[C:7]([Cl:23])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 693426474-tert-butyl-2-chloro-N-[2-(4-fluoro-phenyl)-ethyl]-benzamide

Product 1

HCID 69342921(4-Tert-butyl-2-chloro-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amineYield 74.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1.78 ml (1.78 mmol) of a 1M borane-THF complex solution in THF were added under nitrogen at rt to 198 mg (0.59 mmol) of 4-tert-butyl-2-chloro-N-[2-(4-fluoro-phenyl)-ethyl]-benzamide dissolved in 3 ml THF. The reaction mixture was heated to reflux over night. At rt 5 ml 2N aqueous HCl solution were added and the reaction mixture was heated to reflux for 3 h. The reaction mixture was basified with 7 ml 2N aqueous NaOH solution and extracted twice with diethyl ether. The combined organic layers were washed with saturated aqueous NaCl solution, dried over sodium sulfate, filtered and the solvent was evaporated. The residue was purified by column chromatography (5 g silica gel; DCM/methanol 19:1) to yield 141 mg (67%) of (4-tert-butyl-2-chloro-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amine as a yellow oil. 1H NMR (DMSO-d6, 300 MHz): δ 7.40-7.22 (m, 5H), 7.09 (t, 2H), 3.74 (s, 2H), 2.73 (s, 4H), 1.26 (s, 9H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux over night
  3. temperaturethe reaction mixture was heated
  4. temperatureto reflux for 3 h
  5. extractionextracted twice with diethyl ether
  6. washThe combined organic layers were washed with saturated aqueous NaCl solution
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customthe solvent was evaporated
  10. customThe residue was purified by column chromatography (5 g silica gel; DCM/methanol 19:1)

Sources & evidence

ORD record
ord-ac6b8d3177db4a9d88757aeb40e9042a
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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