[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([NH:12][C@H:13]([C:21]([OH:23])=O)[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[CH2:25][N:26](CC)CC.ClC(OCC(C)C)=O.Cl.CN>C1COCC1.O>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([NH:12][C@H:13]([C:21]([NH:26][CH3:25])=[O:23])[CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[O:11])=[O:7])([CH3:2])([CH3:3])[CH3:4]
To a solution of t-boc-gly-phe 7a (5.3 g, 1.6×10-2 mole) in dry THF (80 ml) under argon at -10° C. is added in turn Et3N (2.5 ml, 1.8×10-2 mole) and isobutyl chloroformate (2.4 ml, 1.8×10-2 mole). The resulting mixture is stirred at -10° C. for 10 minutes before a freshly neutrallized mixture of methylamine hydrochloride (3.3 g, 4.9×10-2 mole), Et3N (6.9 ml, 4.9×10-2 mole), THF (80 ml), and H2O (40 ml) is added in one portion. The cooling bath is then removed and the mixture allowed to warm to room temperature. After stirring overnight the reaction is quenched into saturated aqueous NaHCO3. The aqueous alkaline mixture is extracted with Et2O (3 times) and CH2Cl2 (2 times). The ethereal extracts are combined and subsequently washed with saturated aqueous NaCl as are the CH2Cl2 extracts. The ethereal and CH2Cl2 extracts are then combined and dried over Na2SO4. Filtration of the drying agent and evaporation of the filtrate gives a yellowish foam which when triturated with Et2O affords 8a as a colorless solid which crystallizes from aqueous ethanol as colorless matted needles, 4.1 g (74%), m.p. 158°-160° C. In a similar fashion, t-boc-gly-phe-leu-NHEt is prepared from 7a and leucine ethylamide.
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