반응 #336605

반응 방정식

L-phenylalanine methyl ester

water

CO2

carbonyldiimidazole

N-benzyloxycarbonyl-glycine

→

N-Benzyloxycarbonyl-glycyl-L-phenylalanine Methyl Ester

용매

THF

tetrahydrofuran

반응 조건

후처리

1. 1
   온도The reaction temperature was maintained below 40° C. by application of a water bath to the exterior of the reaction vessel
2. 2
   workup.WAITthe resulting solution was left
3. 3
   농축The reaction mixture was concentrated in vacuo
4. 4
   workup.DISSOLUTIONthe residual oil was dissolved in ethyl acetate (~1 L)
5. 5
   추출This ethyl acetate solution was extracted with 1 N HCI (2×300 mL
6. 6
   추출the first aqueous extract
7. 7
   workup.ADDITIONby addition of 6 N HCl), water (300 mL), saturated aqueous sodium carbonate (300 mL), half-saturated aqueous sodium carbonate (250 mL), and brine (250 mL)
8. 8
   건조The organic phase was dried by filtration through magnesium sulfate and sodium sulfate
9. 9
   농축concentrated in vacuo to constant weight

실험 절차

Solid carbonyldiimidazole (79.10 g, 0.488 mol) was added to a room temperature solution of N-benzyloxycarbonyl-glycine (117.11 g, 0.560 mol) in anhydrous tetrahydrofuran (THF, 600 mL). The resulting solution was stirred for 45 minutes until CO2 evolution had ceased. A solution of L-phenylalanine methyl ester (79.65 g, 0.444 mol) in anhydrous THF (~200 mL) was then added. The reaction temperature was maintained below 40° C. by application of a water bath to the exterior of the reaction vessel. After two hours, a small portion of water (1.5 mL, ~0.08 mol) was added to the reaction mixture to hydrolyze any remaining acylimidazolides and the resulting solution was left to stir overnight. The reaction mixture was concentrated in vacuo and the residual oil was dissolved in ethyl acetate (~1 L). This ethyl acetate solution was extracted with 1 N HCI (2×300 mL--the first aqueous extract was acidified a pH of 1 by addition of 6 N HCl), water (300 mL), saturated aqueous sodium carbonate (300 mL), half-saturated aqueous sodium carbonate (250 mL), and brine (250 mL). The organic phase was dried by filtration through magnesium sulfate and sodium sulfate and concentrated in vacuo to constant weight. Field desorption mass spectrometry (FDMS) of the resulting oil (160.88 g, ~0.434 mol, 98%) indicated the presence of a single component (M+=370). This material was not further purified, but was instead converted directly into cyclo-glycyl-L-phenylalanine (8) by catalytic hydrogenation (vide infra).

출처