Reaktion #550050

Reaktionsgleichung

N-methylmorpholine

Z-Thr(tBu)-Thr(tBu)-Lys(Boc)-OPh

Z-Ile-OH

isobutyl chloroformate

N-methylmorpholine

Tos-OH.H2O

→

N-Benzyloxycarbonyl-L-isoleucyl-O-t-butyl-L-threonyl-O-t-butyl-L-threonyl-Nε -t-butyloxycarbonyl-L-lysine phenyl ester

Lösungsmittel

DMF

DMF

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Filtrationwas filtered off
2. 2
   Temperaturquickly cooled to -20° C
3. 3
   workup.STIRRINGThe reaction mixture was stirred for 15 min. at -15° C. and 1 h at 25° C.
4. 4
   Sonstigeevaporated in vacuo
5. 5
   workup.DISSOLUTIONThe residue was dissolved in 3 l ethyl acetate
6. 6
   Waschenwashed with 10% Na2CO3 sol. (2×1.5 l)
7. 7
   Trocknen, dried over Na2SO4
8. 8
   Filtrationfiltered
9. 9
   Sonstigeevaporated in vacuo
10. 10
    SonstigeThe residue was crystallized from ethyl acetate (2 l)/ether (2 l)

Vorschrift

A solution of Z-Thr(tBu)-Thr(tBu)-Lys(Boc)-OPh (346.9 g, 450 mmol) in 1 l DMF was hydrogenated in the presence of Tos-OH.H2O (85.6 g, 450 mmol) and 10% Pd-C. After the hydrogenation was completed the catalyst was filtered off. Z-Ile-OH (132.66, 500 mmol) was dissolved in 700 ml DMF and cooled to -35° C. While stirring at -35° C., N-methylmorpholine (55 ml, 500 mmol) was added, followed by the addition of isobutyl chloroformate (65 ml, 500 mmol). The reaction mixture was activated for 5 min. at -15° C. and quickly cooled to -20° C. The precooled DMF solution (-25° C.) from the hydrogenation step and N-methylmorpholine (50 ml, 450 mmol) were added simultaneously. The reaction mixture was stirred for 15 min. at -15° C. and 1 h at 25° C. and evaporated in vacuo. The residue was dissolved in 3 l ethyl acetate and washed with 10% Na2CO3 sol. (2×1.5 l), satd. NaCl-sol. (1×1 l), 5% KHSO4 /10% K2SO4 sol. (2×1.5 l) and satd. NaCl-sol., dried over Na2SO4, filtered and evaporated in vacuo. The residue was crystallized from ethyl acetate (2 l)/ether (2 l).

Quelle