反応式
[F:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1.[C:11](OC)(=[O:14])[CH:12]=[CH2:13].CC([O-:21])(C)C.[K+].[CH2:23]1[CH2:27][O:26][CH2:25][CH2:24]1.Cl>C1COCC1.C(=O)=O.CCO>[CH3:25][O:26][C:27]([C:23]1[CH2:24][C:8]([C:9]#[N:10])([C:5]2[CH:6]=[N:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:13][CH2:12][C:11]=1[OH:14])=[O:21]参加物
反応物 4
生成物 1
試薬・触媒・溶媒 2
反応条件
- 温度
- -70 °C
実験手順
To a solution of (6-fluoro-pyridin-3-yl)-acetonitrile (15 g, 0.11 mol) and methyl acrylate (19 g, 0.22 mol) in dry THF (150 mL) cooled to −70° C. in dry ice-EtOH bath was added t-BuOK-THF solution (1M, 330 mL, 0.33 mol) in portions. The reaction mixture was stirred at −70° C. for 4 h. After completion (LCMS) 1N HCl (aq) was added slowly at −70° C. (the temperature of reaction mixture don't rise above −50° C.) to adjust the pH to 5-6. The THF layer was separated and the aqueous phase was extracted with EtOAc (2×150 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to provide the crude title compound (32 g), which was used directly for the next step.
後処理
- customthe temperature of reaction mixture don't rise above −50° C.)
- customThe THF layer was separated
- extractionthe aqueous phase was extracted with EtOAc (2×150 mL)
- washThe combined organic layers were washed with brine
- dry with materialdried over anhydrous sodium sulphate
- filtrationfiltered
- concentrationconcentrated under reduced pressure
出典と根拠
- ORDレコード
- ord-d9f87cf64d314f93b46430131ebd9c92
- 出典データセット
- uspto-grants-2015_08
- 特許番号
- US09102591B2
関連ノート
読み込み中…