(Z)-2-Methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-acrylic Acid → Aleglitazar
반응식
[CH3:1][O:2]/[C:3](=[CH:7]\[C:8]1[C:13]2[S:14][CH:15]=[CH:16][C:12]=2[C:11]([O:17][CH2:18][CH2:19][C:20]2[N:21]=[C:22]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[O:23][C:24]=2[CH3:25])=[CH:10][CH:9]=1)/[C:4]([OH:6])=[O:5].[H][H]>CO.ClCCl>[CH3:1][O:2][C@@H:3]([CH2:7][C:8]1[C:13]2[S:14][CH:15]=[CH:16][C:12]=2[C:11]([O:17][CH2:18][CH2:19][C:20]2[N:21]=[C:22]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[O:23][C:24]=2[CH3:25])=[CH:10][CH:9]=1)[C:4]([OH:6])=[O:5]참가 물질
4
실험 절차
In an analogous manner to Example 10 but in the presence of (S)-phenylethylamine (2.29 mmol) instead of NaOH as a base, 5 g (11.48 mmol) of (Z)-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-acrylic acid were asymmetrically hydrogenated in 37 ml methanol/dichloromethane (3:2) in the presence of 0.93 mg of [Ru(OAc)2((S)-TMBTP)] (S/C molar ratio 10'000) under 30 bar of hydrogen for 4 h at 40°, then 2 h at 60° h to reach 99.9% conversion. Rotary evaporation of the reaction mixture afforded quantitatively (S)-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionic acid of 91.8% ee with 99.4% purity (HPLC area). In analogy to example 13, the experiments described in table 1 have been carried out with different substrate-to-catalyst ratios.