反応式
[CH2:1]([N:8]1[C:12](=[O:13])[CH2:11][C:10]([F:15])(F)[C:9]1=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[F-].CO[CH2:21][N:22]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:23][Si](C)(C)C>C(#N)C>[CH2:1]([N:8]1[C:9](=[O:16])[C@:10]2([F:15])[C@@H:11]([CH2:21][N:22]([CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:23]2)[C:12]1=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1参加物
実験手順
To a solution of 1-benzyl-3,3-difluoropyrrolidine-2,5-dione (325 mg, 1.44 mmol) in acetonitrile (3.6 mL), LiF (56 mg, 1.50 eq) and a stir bar were added. The reaction mixture was sonicated for 2.5 hr at rt. N-(Methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (0.4 mL, 1.59 mmol, 1.10 eq) and LiF (37 mg, 1.44 mmol, 1 eq) were added and continued to sonicate for 0.5 hr. The reaction mixture was concentrated and the salt was removed by filtration. The crude residue was purified by column chromatography and eluted with 2 to 20% EtOAc/heptane and purified further with 2 to 10% EtOAc/heptane. The desired fractions were faintly ultraviolet active but were visualized with KMNO4 stain. The title compound was isolated as a yellow oil (196 mg, 40% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.10-7.43 (m, 10 H) 4.57-4.75 (m, 2 H) 3.63 (s, 2 H) 3.56-3.65 (m, 1 H) 3.33-3.41 (m, 1 H) 3.13 (d, J=9.29 Hz, 1 H) 2.74 (dd, J=9.35, 7.03 Hz, 1 H) 2.57-2.70 (m, 1 H). m/z (APCI+) for C20H20FN2O2 339.20 (M+H)+.
後処理
- customThe reaction mixture was sonicated for 2.5 hr at rt
- customto sonicate for 0.5 hr
- concentrationThe reaction mixture was concentrated
- customthe salt was removed by filtration
- customThe crude residue was purified by column chromatography
- washeluted with 2 to 20% EtOAc/heptane
- custompurified further with 2 to 10% EtOAc/heptane
出典と根拠
- ORDレコード
- ord-682af41dad7142ed9d919f31d9f67340
- 出典データセット
- uspto-grants-2016_03
- 特許番号
- US09290496B2
関連ノート
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