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

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 (1 M, 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]+).

1. waitthe reaction mixture was then left
2. filtrationThe reaction mixture was then filtered
3. washwashed in turn with saturated aq. NaHCO3 (250 ml×3), H2O (250 ml), dilute aq. HCl (1 M, 250 ml×3) and water (250 ml×2)
4. dry with materialThe organic layer was dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo to an oil which
7. customsubsequently crystallised
8. customRecrystallisation from ethyl acetate/hexane

ORD record

ord-d834726b3f4b4f369343abd3b28c594a

Source dataset

uspto-grants-1986_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04568666