Oxalyl chloride → 4-fluoro-N-((1RS,2SR)-2-(4-fluorophenyl)-2-hydroxy-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-1-naphthalenecarboxamide

To a solution of 4-fluoro-1-naphthalenecarboxylic acid (163 mg), 0.86 mmol) in tetrahydrofuran (5 ml) were added oxalyl chloride (0.15 ml, 1.72 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 (200 mg, 0.57 mmol) and saturated aqueous sodium hydrogen carbonate (5 ml) and the mixture was stirred at room temperature for 2 hrs. 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 (214 mg, 77%).

1. customThe reaction solution was evaporated under reduced pressure
2. stirringthe mixture was stirred at room temperature for 2 hrs
3. extractionextracted with ethyl acetate (50 ml×2)
4. washThe extract was washed with saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. customevaporated under reduced pressure
7. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1)
8. customrecrystallized from ethyl acetate-hexane

ORD record

ord-fb7b5d6e8a3e4b8cb430c7db590f237f

Source dataset

uspto-grants-2006_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06982348B2