반응 #314339

반응 방정식

{[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

수율 93.8%

용매

dichloromethane

반응 조건

후처리

1. 1
   온도cooled in an ice bath
2. 2
   농축The reaction mixture was concentrated in vacuo
3. 3
   workup.DISSOLUTIONdissolved in dichloromethane (1 mL)
4. 4
   기타the crude trifluoroacetate salt precipitated with ether (5 mL) and pentane (10 mL)
5. 5
   기타The precipitate was triturated
6. 6
   여과then filtered
7. 7
   workup.ADDITIONadded
8. 8
   기타to form a clear solution
9. 9
   세척The solution was washed with saturated aqueous sodium hydrogen carbonate (2×50 mL)
10. 10
    기타the layers separated
11. 11
    추출the aqueous layer extracted with dichloromethane (4×50 mL)
12. 12
    건조The combined organic extracts were dried over sodium sulfate
13. 13
    여과filtered
14. 14
    농축concentrated in vacuo
15. 15
    기타The resulting solid was triturated with a mixture of ether (1 mL) and pentane (5 mL)
16. 16
    여과filtered
17. 17
    기타dried

실험 절차

{[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%).

출처