Reaktion #1964419

Reaktionsgleichung

sodium carbonate

methyl 4-aminobenzoate

sodium iodide

sodium hydroxide

3-[chloro(cyclohexyl)methyl]-2-methyl-5-phenylthiophene

Hydrochloric acid

→

title compound

Ausbeute 84.2%

4-{[cyclohexyl(2-methyl-5-phenylthiophen-3-yl)methyl]amino}benzoic acid

Ausbeute 84.2%

Lösungsmittel

N,N-dimethylacetamide

ethanol

tetrahydrofuran

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 saturated brine
5. 5
   Trocknendried over magnesium sulfate
6. 6
   Einengenconcentrated under reduced pressure
7. 7
   SonstigeThe residue was purified by silica gel column chromatography (30% ethyl acetate/hexane)
8. 8
   Sonstigeto give a white solid
9. 9
   workup.ADDITIONwas added
10. 10
    workup.STIRRINGthe mixture was stirred
11. 11
    Temperaturheated
12. 12
    Temperaturunder reflux for 2.5 hr
13. 13
    workup.STIRRINGthe mixture was further stirred
14. 14
    Temperaturwith heated
15. 15
    Temperaturunder reflux for 1 hr
16. 16
    Einengenconcentrated under reduced pressure
17. 17
    workup.DISSOLUTIONThe residue was dissolved in water (50 mL)
18. 18
    workup.ADDITION1N hydrochloric acid (15 mL) was added at 0° C
19. 19
    FiltrationThe resulting precipitate was collected by filtration
20. 20
    workup.DISSOLUTIONthe obtained white solid was dissolved in ethyl acetate
21. 21
    WaschenThe solution was washed with saturated brine
22. 22
    Trocknendried over magnesium sulfate
23. 23
    Einengenconcentrated under reduced pressure

Vorschrift

To a mixture of 3-[chloro(cyclohexyl)methyl]-2-methyl-5-phenylthiophene (1.08 g) synthesized above, methyl 4-aminobenzoate (1.07 g), sodium iodide (1.06 g) and N,N-dimethylacetamide (20 mL) was added sodium carbonate (668 mg), and the mixture was stirred overnight at 100° C. under an argon atmosphere. 1N Hydrochloric acid was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (30% ethyl acetate/hexane) to give a white solid. To a mixture of the obtained solid, tetrahydrofuran (10 mL) and ethanol (10 mL) 1N aqueous sodium hydroxide solution (10 mL) was added, and the mixture was stirred heated under reflux for 2.5 hr. 1N Aqueous sodium hydroxide solution (5 mL) was added again, and the mixture was further stirred with heated under reflux for 1 hr, and concentrated under reduced pressure. The residue was dissolved in water (50 mL), and 1N hydrochloric acid (15 mL) was added at 0° C. The resulting precipitate was collected by filtration, and the obtained white solid was dissolved in ethyl acetate. The solution was washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure to give the title compound (1.21 g, 84%) as a pale-yellow solid.

Quelle