반응 #1095116

반응 방정식

oxalyl chloride

hydrochloric acid

hydrochloric acid

2-(2-benzo[b]thiophen-5-ylethoxy)-acetic acid

DL-alaninol

→

2-{[2-(2-benzo[b]thiophen-5-ylethoxy)ethyl]amino}-1-propanol

용매

tetrahydrofuran

tetrahydrofuran

N,N-dimethylformamide

methylene chloride

triethylamine

반응 조건

후처리

1. 1
   workup.ADDITIONare added to the solution
2. 2
   기타obtained above, and the mixture
3. 3
   온도After cooling the mixture to −50° C.
4. 4
   기타the mixture thus formed
5. 5
   workup.STIRRINGis stirred at ambient temperature for 4 hours
6. 6
   기타the organic layer is separated
7. 7
   세척The organic layer is washed with saturated aqueous solution of sodium chloride
8. 8
   건조dried over anhydrous magnesium sulfate
9. 9
   workup.DISTILLATIONthe solvent is distilled off under reduced pressure
10. 10
    기타The residue thus obtained
11. 11
    온도cooled with ice, to which
12. 12
    기타The mixture thus obtained
13. 13
    workup.STIRRINGis stirred at ambient temperature for 13 hours
14. 14
    온도heated
15. 15
    온도under reflux for one hour
16. 16
    온도After cooling the reaction mixture
17. 17
    workup.DISTILLATIONthe solvent is distilled off under reduced pressure, water and ethyl acetate
18. 18
    workup.ADDITIONare added to the residue
19. 19
    기타the aqueous layer is separated
20. 20
    workup.ADDITIONEthyl acetate is added to the aqueous layer
21. 21
    기타the organic layer is separated
22. 22
    기타The organic layer thus obtained
23. 23
    세척is washed with saturated aqueous solution of sodium chloride
24. 24
    건조dried over anhydrous magnesium sulfate
25. 25
    workup.DISTILLATIONthe solvent is distilled off under reduced pressure
26. 26
    기타an oily residue thus obtained
27. 27
    기타is purified by column chromatography (eluent: chloroform:methanol=40:1 to 30:1)

실험 절차

In 10 mL of methylene chloride is dissolved 1.0 g of 2-(2-benzo[b]thiophen-5-ylethoxy)-acetic acid. At an ice-cooled temperature, 0.41 mL of oxalyl chloride and 0.1 mL of N,N-dimethylformamide are added to the solution obtained above, and the mixture is stirred at ambient temperature for 1.5 hours. After cooling the mixture to −50° C., 0.41 mL of DL-alaninol and 1.77 mL of triethylamine are dropwise added, and the mixture thus formed is stirred at ambient temperature for 4 hours. Ice water is added to the reaction mixture, pH is adjusted to 1 with 6 mol/L hydrochloric acid, and the organic layer is separated. The organic layer is washed with saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. The residue thus obtained is dissolved in 10 mL of tetrahydrofuran and cooled with ice, to which is dropwise added 16.9 mL of 1 mol/L solution of borane-tetrahydrofuran complex in tetrahydrofuran. The mixture thus obtained is stirred at ambient temperature for 13 hours. The reaction mixture is acidified with 5.6 mL of 6 mol/L hydrochloric acid and heated under reflux for one hour. After cooling the reaction mixture, the solvent is distilled off under reduced pressure, water and ethyl acetate are added to the residue, and the aqueous layer is separated. Ethyl acetate is added to the aqueous layer, pH is adjusted to 9.5 with 50% aqueous solution of sodium hydroxide, and the organic layer is separated. The organic layer thus obtained is washed with saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, the solvent is distilled off under reduced pressure, and an oily residue thus obtained is purified by column chromatography (eluent: chloroform:methanol=40:1 to 30:1) to obtain 0.80 g of 2-{[2-(2-benzo[b]thiophen-5-ylethoxy)ethyl]amino}-1-propanol as a light yellow-colored oily product.

출처