[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:19]([OH:21])=O)[C@H:13]([C:15]([F:18])([F:17])[F:16])[CH3:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:22][C:23]1[CH:24]=[C:25]([CH2:30][C@H:31]([CH3:37])[C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:26]=[CH:27][C:28]=1[Cl:29].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O>CN(C=O)C.N1C=CC=CC=1>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:19]([NH:22][C:23]1[CH:24]=[C:25]([CH2:30][C@H:31]([CH3:37])[C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:26]=[CH:27][C:28]=1[Cl:29])=[O:21])[C@H:13]([C:15]([F:16])([F:17])[F:18])[CH3:14])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=11.26 g (purity 76%, about 3.14 mmol) of (3R)—N-[(benzyloxy)carbonyl]-4,4,4-trifluorovaline (diastereomer mixture) and 0.91 g (3.76 mmol) of (+)-ethyl (2S)-3-(3-amino-4-chlorophenyl)-2-methylpropanoate were dissolved in a mixture of 10 ml of DMF and 4 ml of pyridine, and 1.55 g (4.08 mmol) of HATU were added at RT. The reaction mixture was stirred at RT overnight and then added to water. The mixture was extracted three times with ethyl acetate, and the combined organic phases were then washed successively with sat. sodium bicarbonate solution, 1 N hydrochloric acid and sat. sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The resulting solid was stirred in a mixture of cyclohexane and diethyl ether (about 3:1), filtered off with suction and dried under high vacuum. This gave 0.99 g of the target product (59.9% of theory, diastereomer ratio about 7:1).
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