[C:1]([NH:4][C:5]1[S:6][CH:7]=[C:8]([CH2:10][CH2:11][C:12]2[CH:20]=[CH:19][C:15]([C:16](O)=[O:17])=[C:14]([F:21])[CH:13]=2)[N:9]=1)(=[O:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[BH4-].[Na+].O>O1CCCC1>[F:21][C:14]1[CH:13]=[C:12]([CH2:11][CH2:10][C:8]2[N:9]=[C:5]([NH:4][C:1](=[O:3])[CH3:2])[S:6][CH:7]=2)[CH:20]=[CH:19][C:15]=1[CH2:16][OH:17]To a suspension of 4-{2-[2-(acetylamino)-1,3-thiazol-4-yl]ethyl}-2-fluorobenzoic acid (555.0 mg, 1.800 mmol) in anhydrous tetrahydrofuran (4 ml) was added 1,1′-carbonyldiimidazole (364.8 mg, 2.250 mmol), and the mixture was stirred at room temperature for 1.5 hr. The reaction mixture was added dropwise to a mixture of sodium borohydride (1.362 g, 36.0 mmol), tetrahydrofuran (36 ml) and water (9 ml), which had been cooled to −25° C. After stirring at not more than 0° C. for 1 hr, water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The combined organic layer was washed with 1M hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure, and a mixture of methanol (0.5 ml) and diisopropyl ether (15 ml) was added to the residue. The precipitate was collected by filtration and dried under reduced pressure to give N-(4-{2-[3-fluoro-4-(hydroxymethyl)phenyl]ethyl}-1,3-thiazol-2-yl)acetamide (342.8 mg, 1.165 mmol, yield 64.7%) as a white solid.
불러오는 중…
