반응 #1964419

반응 방정식

sodium carbonate

methyl 4-aminobenzoate

sodium iodide

sodium hydroxide

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

Hydrochloric acid

→

title compound

수율 84.2%

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

수율 84.2%

용매

N,N-dimethylacetamide

ethanol

tetrahydrofuran

반응 조건

후처리

1. 1
   기타to quench
2. 2
   기타the reaction
3. 3
   추출the mixture was extracted with ethyl acetate
4. 4
   세척The extract was washed with saturated brine
5. 5
   건조dried over magnesium sulfate
6. 6
   농축concentrated under reduced pressure
7. 7
   기타The residue was purified by silica gel column chromatography (30% ethyl acetate/hexane)
8. 8
   기타to give a white solid
9. 9
   workup.ADDITIONwas added
10. 10
    workup.STIRRINGthe mixture was stirred
11. 11
    온도heated
12. 12
    온도under reflux for 2.5 hr
13. 13
    workup.STIRRINGthe mixture was further stirred
14. 14
    온도with heated
15. 15
    온도under reflux for 1 hr
16. 16
    농축concentrated 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
    여과The resulting precipitate was collected by filtration
20. 20
    workup.DISSOLUTIONthe obtained white solid was dissolved in ethyl acetate
21. 21
    세척The solution was washed with saturated brine
22. 22
    건조dried over magnesium sulfate
23. 23
    농축concentrated under reduced pressure

실험 절차

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.

출처