Reacción #1095116

Ecuación de reacción

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

Disolventes

tetrahydrofuran

tetrahydrofuran

N,N-dimethylformamide

methylene chloride

triethylamine

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONare added to the solution
2. 2
   Otroobtained above, and the mixture
3. 3
   TemperaturaAfter cooling the mixture to −50° C.
4. 4
   Otrothe mixture thus formed
5. 5
   workup.STIRRINGis stirred at ambient temperature for 4 hours
6. 6
   Otrothe organic layer is separated
7. 7
   LavadoThe organic layer is washed with saturated aqueous solution of sodium chloride
8. 8
   Secadodried over anhydrous magnesium sulfate
9. 9
   workup.DISTILLATIONthe solvent is distilled off under reduced pressure
10. 10
    OtroThe residue thus obtained
11. 11
    Temperaturacooled with ice, to which
12. 12
    OtroThe mixture thus obtained
13. 13
    workup.STIRRINGis stirred at ambient temperature for 13 hours
14. 14
    Temperaturaheated
15. 15
    Temperaturaunder reflux for one hour
16. 16
    TemperaturaAfter 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
    Otrothe aqueous layer is separated
20. 20
    workup.ADDITIONEthyl acetate is added to the aqueous layer
21. 21
    Otrothe organic layer is separated
22. 22
    OtroThe organic layer thus obtained
23. 23
    Lavadois washed with saturated aqueous solution of sodium chloride
24. 24
    Secadodried over anhydrous magnesium sulfate
25. 25
    workup.DISTILLATIONthe solvent is distilled off under reduced pressure
26. 26
    Otroan oily residue thus obtained
27. 27
    Otrois purified by column chromatography (eluent: chloroform:methanol=40:1 to 30:1)

Procedimiento

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.

Fuente