反応 #336605

反応方程式

L-phenylalanine methyl ester

water

CO2

carbonyldiimidazole

N-benzyloxycarbonyl-glycine

→

N-Benzyloxycarbonyl-glycyl-L-phenylalanine Methyl Ester

溶媒

THF

tetrahydrofuran

反応条件

後処理

1. 1
   温度The 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
   濃縮The reaction mixture was concentrated in vacuo
4. 4
   workup.DISSOLUTIONthe residual oil was dissolved in ethyl acetate (~1 L)
5. 5
   抽出This ethyl acetate solution was extracted with 1 N HCI (2×300 mL
6. 6
   抽出the 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
   乾燥The organic phase was dried by filtration through magnesium sulfate and sodium sulfate
9. 9
   濃縮concentrated in vacuo to constant weight

実験手順

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).

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