C([Li])CCC.[S:6]1[CH:10]=[CH:9][N:8]=[CH:7]1.[CH3:11][C:12]([CH3:25])([O:14][C:15]([NH:17][C@H:18]([CH:23]=[O:24])[CH2:19][CH:20]([CH3:22])[CH3:21])=[O:16])[CH3:13]>CCCCCC.O1CCCC1>[CH3:13][C:12]([CH3:25])([O:14][C:15]([NH:17][C@@H:18]([CH2:19][CH:20]([CH3:21])[CH3:22])[CH:23]([C:7]1[S:6][CH:10]=[CH:9][N:8]=1)[OH:24])=[O:16])[CH3:11]2.5 n-Butyllithium in hexane (8 ml.) is added to a solution containing thiazole (1.7 g., 20 mmole) in dry tetrahydrofuran (60 ml.) cooled to -70° under argon. After stirring a short time, the solid material begins to come out of solution. The reaction remains heterogeneous after 35 minutes at -40° to -35° . After cooling the reaction to -50° , a solution containing N-[(1,1-dimethylethoxy)carbonyl]-L-leucinal (2.2g., 10 mmole) in tetrahydrofuran (5 ml.) is added. After 90 minutes the reaction is warmed to -10° and quenched with saturated ammonium chloride (10 ml.). The reaction mixture is extracted into ether and the organic extract is rinsed with water and brine, dired (MgSO4) and concentrated in vacuo to give 1.8 g. of amide product. Two flash chromatographies on first 100 g. and then 150 g. of silica gel (LPS-1) eluting with petroleum ether:acetone (20:1 ) fails to remove a minor impurity from the co-eluting desired diastereimeric product mixture. A total of 1.2 g. of (2S)-2-[[(1,1-dimethylethoxy)carbonyl]amino]-4-methyl-1-(2-thiazolyl)-1-pentanol is obtained. TLC (silica gel; petroleum ether:acetone, 4:1) Rf =0.37. 8 α]D =-38.6° (c=1, chloroform).
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