Reaktion #1964177

Reaktionsgleichung

3-[chloro(cyclohexyl)methyl]-2-ethyl-5-[4-(trifluoromethyl)phenyl]thiophene

ammonium chloride

methyl 4-aminobenzoate

sodium iodide

sodium carbonate

sodium hydroxide

Hydrochloric acid

→

title compound

Ausbeute 29.3%

4-[(cyclohexyl{2-ethyl-5-[4-(trifluoromethyl)phenyl]thiophen-3-yl}methyl)amino]benzoic acid

Ausbeute 29.3%

Lösungsmittel

N,N-dimethylacetamide

ethanol

tetrahydrofuran

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeto quench
2. 2
   Sonstigethe reaction
3. 3
   Extraktionthe mixture was extracted with ethyl acetate
4. 4
   WaschenThe extract was washed with brine
5. 5
   Trocknendried over magnesium sulfate
6. 6
   Einengenconcentrated under reduced pressure
7. 7
   Sonstigeto give a dark-brown oil
8. 8
   workup.STIRRINGthe mixture was stirred at 60° C. for 1 hr
9. 9
   workup.STIRRINGstirred
10. 10
    Temperaturwith heating
11. 11
    Temperaturunder reflux for 30 min
12. 12
    Sonstigethe organic solvent was evaporated under reduced pressure
13. 13
    Extraktionthe mixture was extracted with ethyl acetate
14. 14
    WaschenThe extract was washed with brine
15. 15
    Trocknendried over magnesium sulfate
16. 16
    Einengenconcentrated under reduced pressure
17. 17
    SonstigeThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:7, volume ratio)
18. 18
    Sonstigeto give a brown oil
19. 19
    Waschenwashed with 1N hydrochloric acid and brine
20. 20
    Trocknendried over magnesium sulfate
21. 21
    Einengenconcentrated under reduced pressure

Vorschrift

To a mixture of 3-[chloro(cyclohexyl)methyl]-2-ethyl-5-[4-(trifluoromethyl)phenyl]thiophene (1.00 g) synthesized above, methyl 4-aminobenzoate (780 mg), sodium iodide (1.55 g) and N,N-dimethylacetamide (10 mL) was added sodium carbonate (547 mg), and the mixture was stirred under an argon atmosphere at 100° C. overnight. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and concentrated under reduced pressure to give a dark-brown oil. To a mixture of the obtained oil, tetrahydrofuran (10 mL) and ethanol (10 mL) was added 1N aqueous sodium hydroxide solution (10 mL), and the mixture was stirred at 60° C. for 1 hr, and stirred with heating under reflux for 30 min. 1N Hydrochloric acid (10 mL) was added to the reaction mixture, the organic solvent was evaporated under reduced pressure, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:7, volume ratio) to give a brown oil. The obtained oil was dissolved in ethyl acetate, washed with 1N hydrochloric acid and brine, dried over magnesium sulfate and concentrated under reduced pressure to give the title compound (369 mg, 29%) as a pale-brown solid.

Quelle