Tetrahydrofuran → 4-Benzylmorpholin-3-one
反応式
[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][C:9]1=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([N-]C(C)C)(C)C.[Li+].[CH2:23]1[CH2:27][O:26][CH2:25][CH2:24]1>>[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH:25]([CH:24]2[CH2:23][CH2:27]2)[OH:26])[C:9]1=[O:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1.[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][C:9]1=[O:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1参加物
5
反応条件
- 温度
- -78 °C
実験手順
To a solution of 4-benzyl-morpholin-3-one (9.5 g, 50 mmol) in THF (200 mL) is added lithium diisopropylamide (2M solution in THE, 27 mL, 54 mmol, 1.1 eq) dropwise over 20 minutes at −78° C. followed by slow addition of cyclopropyl methylaldehyde (3.85 mL, 55 mmol, 1.1 eq). After stirring at −78° C. for one hour the reaction mixture is allowed to warm to room temperature and stirred for another 6 hours. The reaction is quenched by addition of EtOAc and brine. The aqueous layer is extracted with EtOAc, the combined organic layers are dried over magnesium sulphate and reduced in vacuo. Purification using automated column chromatography (DCM/MeOH, 100/0 to 85/15 [v/v]) gives 75 in 70% purity with 4-benzyl-morpholin-3-one as the major impurity. This product is directly used in the next step. MW 261.32; C15H19NO3; LCMS (6 min method) m/z 261.32 [M+H]+, RT 2.23