反応式
F[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]([F:13])([F:12])[F:11])[C:3]=1[CH3:14].[NH2:15][C@H:16]([C:20]([OH:23])([CH3:22])[CH3:21])[C:17]([OH:19])=[O:18].C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([NH:15][C@H:16]([C:20]([OH:23])([CH3:22])[CH3:21])[C:17]([OH:19])=[O:18])=[C:3]([CH3:14])[C:4]=1[C:10]([F:13])([F:12])[F:11])#[N:7]参加物
反応条件
- 温度
- 85 °C
実験手順
4-fluoro-3-methyl-2-(trifluoromethyl)benzonitrile (763 mg, 3.76 mmol) was mixed together with (R)-2-amino-3-hydroxy-3-methylbutanoic acid (500 mg, 3.76 mmol) in DMSO (25 mL). K2CO3 (1.56 g, 11.28 mmol) was added to the reaction mixture and the reaction mixture stirred at 85° C. for 18 h. The reaction mixture was allowed to cool to room temperature, quenched with H2O (25 mL) and extracted with EtOAc (2×30 mL). The aqueous layer was then acidified with solid citric acid and extracted with EtOAc (2×80 mL). The later organic extracts were combined, washed with H2O (2×30 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provided the title compound as a yellow solid (1.15 g, 97%): 1H NMR (400 MHz, d6-acetone, δ in ppm) 7.63 (d, J=9 Hz, 1H), 6.97 (d, J=9 Hz, 1H), 5.62 (d, J=9 Hz, 1H), 4.20 (d, J=9 Hz, 1H), 2.33 (s, 3H), 1.43 (s, 3H) and 1.42 (s, 3H).
後処理
- temperatureto cool to room temperature
- customquenched with H2O (25 mL)
- extractionextracted with EtOAc (2×30 mL)
- extractionextracted with EtOAc (2×80 mL)
- washwashed with H2O (2×30 mL)
- dry with materialdried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated under reduced pressure
出典と根拠
- ORDレコード
- ord-85118c7de333478b8df4fef83b50dd1d
- 出典データセット
- uspto-grants-2014_02
- 特許番号
- US08642632B2
関連ノート
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