반응 #49185

반응 방정식

Compound 44a

2-(6-{2-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-pyrrolidin-1-yl}-6-oxo-hexyl)-isoindole-1,3-dione

ethyl acetate

2-cyanoethyl-N,N,N′,N′-tetraisopropylphosphorodiamidite

toluene

→

compound 45a

수율 89.0%

4-Hydroxy-prolinol phthalimido phosphoramidite

수율 89.0%

용매

dichloromethane

hexane

반응 조건

후처리

1. 1
   건조the mixture was dried over P2O5 in a vacuum oven for overnight at 40° C
2. 2
   workup.DISSOLUTIONThe reaction mixture was dissolved in dichloromethane (20 mL)
3. 3
   세척washed with 5% NaHCO3 (100 mL) and brine (100 mL)
4. 4
   건조The organic layer was dried over anhydrous Na2SO4
5. 5
   여과filtered
6. 6
   농축concentrated under reduced pressure
7. 7
   기타The residue was purified over silica gel (50:49:1, EtOAc:Hexane:triethlyamine)

실험 절차

Compound 44a (9.0 g, 13.57 mmol) was coevaporated with anhydrous toluene (50 mL). To the residue N,N-tetraisopropylammonium tetrazolide (0.766 g, 6.8 mmol) was added and the mixture was dried over P2O5 in a vacuum oven for overnight at 40° C. The reaction mixture was dissolved in dichloromethane (20 mL) and 2-cyanoethyl-N,N,N′,N′-tetraisopropylphosphorodiamidite (6.13 g, 6.7 mL, 20.35 mmol) was added. The reaction mixture was stirred at ambient temperature for overnight. The completion of the reaction was ascertained by TLC (Rf=0.7 in 1:1 ethyl acetate:hexane). The reaction mixture was diluted with dichloromethane (100 mL) and washed with 5% NaHCO3 (100 mL) and brine (100 mL). The organic layer was dried over anhydrous Na2SO4 filtered and concentrated under reduced pressure. The residue was purified over silica gel (50:49:1, EtOAc:Hexane:triethlyamine) to afford compound 45a as white solid (10.5 g, 89%).

출처