반응 #219278

반응 방정식

Compound 17

[3-[8-(3-Bromo-phenyl)-1,4-dioxa-spiro[4.5]dec-8-ylamino]-1-(3,5-difluoro-benzyl)-2-hydroxy-propyl]-carbamic acid tert-butyl ester

N-Methylmorpholine

1-Hydroxylbenzotriazole hydrate

1-Ethyl-3-(3′-Dimethylaminopropyl)carbodiimide Hydrochloride

Acetic Acid

→

N-[3-[8-(3-Bromo-phenyl)-1,4-dioxa-spiro[4.5]dec-8-ylamino]-1-(3,5-difluoro-benzyl)-2-hydroxy-propyl]-acetamide

용매

CH2Cl2

trifluoroacetic acid

반응 조건

후처리

1. 1
   농축concentrated under reduced pressure
2. 2
   workup.DISSOLUTIONThe residue was dissolved in 4 mL CH2Cl2
3. 3
   workup.STIRRINGThe reaction was stirred at 0° C
4. 4
   workup.STIRRINGthe mixture stirred at 0° C. for five min
5. 5
   workup.STIRRINGThe reaction was stirred at room temperature for two h
6. 6
   기타CH2Cl2 was removed by reduced pressure
7. 7
   workup.DISSOLUTIONthe residue dissolved in EtOAc
8. 8
   세척The organic layer was rinsed with a saturated NaHCO3 solution three times and once with Brine
9. 9
   건조The organic layer was dried with MgSO4
10. 10
    여과filtered
11. 11
    농축concentrated under reduced pressure
12. 12
    기타Compound 22 was purified by preparative HPLC

실험 절차

Compound 17 was dissolved in 1 mL (1:1) trifluoroacetic acid (TFA) and CH2Cl2. The reaction stirred at room temperature for 2 h and concentrated under reduced pressure. The residue was dissolved in 4 mL CH2Cl2 and N-Methylmorpholine (NMM) (3.12 mmol). The reaction was stirred at 0° C. Acetic Acid (0.76 mmol) was added slowly to the reaction mixture and the mixture stirred at 0° C. for five min. Then 1-Hydroxylbenzotriazole hydrate (HOBt) (0.76 mmol) and 1-Ethyl-3-(3′-Dimethylaminopropyl)carbodiimide Hydrochloride (EDC.HCl) (0.76 mmol) were added sequentially. The reaction was stirred at room temperature for two h. CH2Cl2 was removed by reduced pressure and the residue dissolved in EtOAc. The organic layer was rinsed with a saturated NaHCO3 solution three times and once with Brine. The organic layer was dried with MgSO4, filtered and concentrated under reduced pressure. Compound 22 was purified by preparative HPLC.

출처