Réaction #1697384

Équation de réaction

6-methoxy-1-naphthalenecarboxylic acid

oxalyl chloride

(1RS,2SR)-1-(4-fluorophenyl)-1-hydroxy-3-(4-(trifluoromethyl)phenyl)-2-propylamine hydrochloride

sodium hydrogen carbonate

→

title compound

Rendement 69.2%

N-((1RS,2SR)-2-(4-fluorophenyl)-2-hydroxy-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-6-(methyloxy)-1-naphthalenecarboxamide

Rendement 69.2%

Solvants

tetrahydrofuran

N,N-dimethylformamide

ethyl acetate

water

Conditions de réaction

Traitement

1. 1
   AutreThe reaction solution was evaporated under reduced pressure
2. 2
   workup.STIRRINGthe mixture was stirred overnight at room temperature
3. 3
   Extractionextracted with ethyl acetate (50 ml×2)
4. 4
   LavageThe extract was washed with saturated brine
5. 5
   Séchagedried over anhydrous magnesium sulfate
6. 6
   Autreevaporated under reduced pressure
7. 7
   AutreThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1)
8. 8
   Autrerecrystallized from ethyl acetate-hexane

Mode opératoire

To a solution of 6-methoxy-1-naphthalenecarboxylic acid (129 mg, 0.64 mmol) in tetrahydrofuran (5 ml) were added oxalyl chloride (0.11 ml, 1.28 mmol) and N,N-dimethylformamide (0.01 ml), and the mixture was stirred at room temperature for 30 min. The reaction solution was evaporated under reduced pressure. To a solution of the residue in ethyl acetate (5 ml) were added (1RS,2SR)-1-(4-fluorophenyl)-1-hydroxy-3-(4-(trifluoromethyl)phenyl)-2-propylamine hydrochloride (150 mg, 0.43 mmol) and saturated aqueous sodium hydrogen carbonate (5 ml) and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (50 ml), and extracted with ethyl acetate (50 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) and recrystallized from ethyl acetate-hexane to give the title compound (148 mg, 69%).

Source