Reacción #314339

Ecuación de reacción

{[4-({Bis-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-carbamoyl}-methoxy)-phenyl]-[1-(6-iodo-1H-benzoimidazol-2-yl)-2-phenyl-propylcarbamoyl]-methyl}-carbamic acid tert-butyl ester

triflouroacetic acid

→

(R)-2-amino-2-(4-{[bis-(2-hydroxy-ethyl)-carbamoyl]-methoxy}-phenyl)-N-[(1S,2S)-1-(6-iodo-1H-benzoimidazol-2-yl)-2-phenyl-propyl]-acetamide

Rendimiento 93.8%

Disolventes

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturacooled in an ice bath
2. 2
   ConcentraciónThe reaction mixture was concentrated in vacuo
3. 3
   workup.DISSOLUTIONdissolved in dichloromethane (1 mL)
4. 4
   Otrothe crude trifluoroacetate salt precipitated with ether (5 mL) and pentane (10 mL)
5. 5
   OtroThe precipitate was triturated
6. 6
   Filtraciónthen filtered
7. 7
   workup.ADDITIONadded
8. 8
   Otroto form a clear solution
9. 9
   LavadoThe solution was washed with saturated aqueous sodium hydrogen carbonate (2×50 mL)
10. 10
    Otrothe layers separated
11. 11
    Extracciónthe aqueous layer extracted with dichloromethane (4×50 mL)
12. 12
    SecadoThe combined organic extracts were dried over sodium sulfate
13. 13
    Filtraciónfiltered
14. 14
    Concentraciónconcentrated in vacuo
15. 15
    OtroThe resulting solid was triturated with a mixture of ether (1 mL) and pentane (5 mL)
16. 16
    Filtraciónfiltered
17. 17
    Otrodried

Procedimiento

{[4-({Bis-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-carbamoyl}-methoxy)-phenyl]-[1-(6-iodo-1H-benzoimidazol-2-yl)-2-phenyl-propylcarbamoyl]-methyl}-carbamic acid tert-butyl ester (270 mg, 0.27 mmol) was dissolved in dry dichloromethane (6 mL) and cooled in an ice bath. To the stirred solution was added triflouroacetic acid (3.12 mL, 40.5 mmol). The reaction mixture was stirred at 0° C. for 1 hour. The reaction mixture was concentrated in vacuo, dissolved in dichloromethane (1 mL) and the crude trifluoroacetate salt precipitated with ether (5 mL) and pentane (10 mL). The precipitate was triturated then filtered. The solid was taken into dichloromethane (50 mL) and tetrahydrofuran added to form a clear solution. The solution was washed with saturated aqueous sodium hydrogen carbonate (2×50 mL), the layers separated and the aqueous layer extracted with dichloromethane (4×50 mL). The combined organic extracts were dried over sodium sulfate filtered and concentrated in vacuo. The resulting solid was triturated with a mixture of ether (1 mL) and pentane (5 mL), filtered and dried to give (R)-2-amino-2-(4-{[bis-(2-hydroxy-ethyl)-carbamoyl]-methoxy}-phenyl)-N-[(1S,2S)-1-(6-iodo-1H-benzoimidazol-2-yl)-2-phenyl-propyl]-acetamide (170 mg, 93.8%).

Fuente