Dicyclohexylcarbodiimide → Ethyl N-(1-((benzyloxy)carbonyl)-L-prolyl)-L-leucinate

Participants

Reaction Steps

To a stirred solution of Z-L-proline (12.7 g, 0.051M) in CH2Cl2 (200 ml) cooled to 0° was added 1-hydroxy benzotriazole (7.0 g) followed by a solution of DCC (10.6 g) in CH2Cl2 (50 ml). After 30 min. at 0° L-leucine ethyl ester (10.0 g, 0.051 molM) was added followed by triethylamine (15 ml) and the reaction mixture was then left to stir and warm up to room temperature overnight. The reaction mixture was then filtered and washed in turn with saturated aq. NaHCO3 (250 ml×3), H2O (250 ml), dilute aq. HCl (1M, 250 ml×3) and water (250 ml×2). The organic layer was dried (Na2SO4), filtered and concentrated in vacuo to an oil which subsequently crystallised. Recrystallisation from ethyl acetate/hexane gave N-(benzyloxycarbonyl)-L-prolyl-L-leucine ethyl ester as a white crystalline solid, 15.5 g, (78%); m.p. 67°-68°; (Found: C,64.55; H,7.79; N,7.22. C21H30N2O5 requires C,64.61; H,7.74; N,7.17%); νmax (CHCl3) 1740 and 1680 cm-1 ; δ(CDCl3) 0.7-0.95 (6H,m,CH(CH3)2); 1.18 (3H,m,OCH2CH3); 1.3-1.95 and 2.05-2.25 (7H,m,CH2CH2, CH2CH(CH3)2); 3.4 (2H,m,CH2N); 4.05 (2H,m,OCH2CH3); 4.25 (2H,m,α--CH); 4.98 and 5.05 (together 2H, respectively q,J=7 Hz, and m, CH2C6H5); 7.35 (5H, broad s, C6H5) and 8.26 (1H,m,CONH); m/e 391 (100%, [m+1]+).

Provenance & Evidence