Ethyl Acrylate → rac-3-[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-propionic acid ethyl ester

HRID 909096ノート

反応式

HRID 909096 の反応式
[Cl:1][C:2]1[C:3]([F:28])=[C:4]([CH:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:10][NH:9]2)[CH:5]=[CH:6][CH:7]=1.[C:29]([O:33][CH2:34][CH3:35])(=[O:32])[CH:30]=[CH2:31].FC(F)(F)S([O-])(=O)=O.[Sm+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>C1COCC1.C(Cl)Cl>[CH2:34]([O:33][C:29](=[O:32])[CH2:30][CH2:31][N:9]1[CH2:10][C@@H:11]([CH2:23][C:24]([CH3:25])([CH3:27])[CH3:26])[C@@:12]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[F:22])([C:13]#[N:14])[C@H:8]1[C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[F:28])[CH3:35]

参加物

6

反応物 3

HCID 8821Ethyl AcrylateHCID 10145316Samarium(III) trifluoromethanesulfonateHCID 67095372rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile

生成物 1

HCID 67095542rac-3-[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-propionic acid ethyl ester収率 32.5%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
160 °C

実験手順

A mixture of rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile (30.6 mg, 0.0723 mmol), ethyl acrylate (73.7 mg, 0.728 mmol, Aldrich) and samarium(III) trifluoromethanesulfonate (34.9 mg, 0.0572 mmol) in THF (1.5 mL) were heated for 3 h at 160° C. in a microwave tube. The reaction mixture was then diluted with CH2Cl2, extracted with water, and saturated NaCl. The organic phase was separated, dried over Na2SO4, and purified by flash column to give rac-3-[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-propionic acid ethyl ester (12.3 mg, 32.5%).

後処理

  1. extractionextracted with water, and saturated NaCl
  2. customThe organic phase was separated
  3. dry with materialdried over Na2SO4
  4. custompurified by flash column

出典と根拠

ORDレコード
ord-abfc3d5ab3c946a180cf725b0ff58d0d
出典データセット
uspto-grants-2011_09
特許番号
US08017607B2

反応ノート

読み込み中…