Tetrahydrofuran → (5R)-3-(4-benzyloxy-3-fluoro-phenyl)-5-hydroxy-methyl-oxazolidin-2-one
反応式
[CH2:1]([O:8][C:9](=[O:26])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:13]([F:25])[CH:12]=1)[C:2]1C=CC=C[CH:3]=1.C([Li])CCC.CCCCCC.[O:38]1CCCC1>>[CH2:18]([O:17][C:14]1[CH:15]=[CH:16][C:11]([N:10]2[CH:2]([CH3:3])[C@H:1]([OH:38])[O:8][C:9]2=[O:26])=[CH:12][C:13]=1[F:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1参加物
5
反応条件
- 温度
- -78 °C
実験手順
A stirred solution of 17.5 g (4-benzyloxy-3-fluoro-phenyl)-carbamic acid benzyl ester (MW: 351.38, 50 mmol) in 30 ml of dry tetrahydrofuran was cooled to −78° C. with a dry ice/acetone bath. 22.8 ml of a 2.3M n-butyl-lithium solution in n-hexane (52.5 mmol) was added drop wise and the reaction mixture stirred at −78° C. for 15 min. 7.92 g R(−)-glycidyl butyrate (MW: 144.17, 60 mmol) were added and the reaction was allowed to warm up to room temperature. The reaction was monitored by HPLC, quenched with a saturated ammonium chloride solution and diluted with 100 ml of ethyl acetate. The organic layer was washed with 200 ml water and 200 ml brine. The organic layer was dried over magnesium sulfate, filtered and the filtrate evaporated under reduced pressure. The residue was crystallized from 200 ml of a 1/1-ethyl acetate/hexane mixture. The solid was collected and recrystallized from 150 ml of a 9/1 ethyl acetate/dichloro-methane mixture. The colorless crystals were collected and dried. Yield: 10.4-g, 65.5%. MS: 318.1 (M+H)+. Method ESI+.