Bromobenzene → 3-[2-(4-Phenoxy-phenyl)-morpholin-4-yl]-propionic acid tert-butyl ester
反応式
C([O-])([O-])=O.[Cs+].[Cs+].[C:7]([O:11][C:12](=[O:28])[CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][O:18][CH:17]([C:21]2[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=2)[CH2:16]1)([CH3:10])([CH3:9])[CH3:8].Br[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>>[C:7]([O:11][C:12](=[O:28])[CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][O:18][CH:17]([C:21]2[CH:22]=[CH:23][C:24]([O:27][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[CH:25][CH:26]=2)[CH2:16]1)([CH3:10])([CH3:8])[CH3:9]参加物
4
反応条件
- 温度
- 140 °C
実験手順
To a mixture of Cs2CO3 (70 mg; 0.21 mmol), 3-[2-(4-Hydroxy-phenyl)-morpholin-4-yl]-propionic acid tert-butyl ester (33.8 mg, 0.11 mmol) and bromobenzene (12.6 μL, 0.12 mmol) was added 0.5 mL of a freshly prepared catalyst stock solution (see below) in a 2-5 mL Biotage® microwave vial. The vial was briefly flushed with N2 and sealed to maintain a semi-inert atmosphere. The resulting mixture was heated for 22 h, at 140° C. After cooling to room temperature, water (5 mL) was added and the mixture was extracted with EtOAc (1×7.5 mL, 2×5 mL). The combined organic layers were concentrated in vacuo, and the residue was purified by preparative TLC (SiO2, CH2Cl2/MeOH 99:1) to afford 3-[2-(4-phenoxy-phenyl)-morpholin-4-yl]-propionic acid tert-butyl ester (49 mg). The catalyst stock solution was prepared as follows: To a suspension of copper(I)iodide (73 mg, 0.16 mmol) in anhydrous toluene (9 mL) was added 1-butylimidazole (127 μL; 120 mg; 0.41 mmol). The solution was purged with N2 for 15 min. and vigorously agitated until all the CuI had fully dissolved.