Hydrochloric Acid → N-(2-(4-fluorophenyl)-2-oxo-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-4-methyl-1-naphthalenecarboxamide

HRID 1610166Notes

Reaction equation

HRID 1610166 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:23])[CH:10]([NH2:22])[CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)=[CH:5][CH:4]=1.[CH3:24][C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:28]([C:35](O)=[O:36])=[CH:27][CH:26]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C1CCN2C(=NCCC2)CC1.Cl>CN(C)C=O.O>[F:2][C:3]1[CH:4]=[CH:5][C:6]([C:9](=[O:23])[CH:10]([NH:22][C:35]([C:28]2[C:29]3[C:34](=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:25]([CH3:24])=[CH:26][CH:27]=2)=[O:36])[CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)=[CH:7][CH:8]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 30142854-Methyl-1-naphthalenecarboxylic acidHCID 222621952-(4-Fluorophenyl)-2-oxo-1-[[4-(trifluoromethyl)phenyl]methyl]ethylamine hydrochloride

Product 1

HCID 22261573N-(2-(4-fluorophenyl)-2-oxo-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-4-methyl-1-naphthalenecarboxamideYield 80.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-fluorophenyl)-1-oxo-3-(4-(trifluoromethyl)phenyl)-2-propylamine hydrochloride (600 mg, 1.73 mmol) and 4-methyl-1-naphthalenecarboxylic acid (354 mg, 1.90 mmol) in N,N-dimethylformamide (10 ml) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (496 mg, 2.59 mmol), 1-hydroxy-1H-benzotriazole (396 mg, 2.59 mmol) and 1,8-diazabicyclo[5.4.0]-7-undecene (0.28 ml, 1.90 mmol) and the mixture was stirred overnight. To the reaction solution were added 1N aqueous hydrochloric acid solution (10 ml) and water (100 ml), and the mixture was extracted with ethyl acetate (50 ml×2): The extract was washed with 1N aqueous sodium hydroxide solution and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1 and recrystallized from ethyl acetate-hexane to give N-(2-(4-fluorophenyl)-2-oxo-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-4-methyl-1-naphthalenecarboxamide (665 mg, 80%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (50 ml×2)
  2. washThe extract was washed with 1N aqueous sodium hydroxide solution and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customevaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane
  6. customethyl acetate=4:1 and recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-0ee8e99b7ece4132b49dffea312f8a23
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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