Ammonium Chloride → (4R,5R)-5-((S)-(5-(4-fluorophenyl)thiophen-2-yl)(hydroxy)methyl)-1-methyl-4-phenylpyrrolidin-2-one
反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][CH:10]=[CH:11][CH:12]=2)=[CH:4][CH:3]=1.[Li]CCCC.[CH:18]([C@@H:20]1[N:24]([CH3:25])[C:23](=[O:26])[CH2:22][C@@H:21]1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:19].[NH4+].[Cl-]>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:9][C:10]([C@@H:18]([OH:19])[C@@H:20]3[N:24]([CH3:25])[C:23](=[O:26])[CH2:22][C@@H:21]3[C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:11][CH:12]=2)=[CH:6][CH:7]=1参加物
反応物 4
生成物 1
試薬・触媒・溶媒 1
反応条件
- 温度
- -20 °C
実験手順
To a −65° C. solution of 2-(4-fluorophenyl)thiophene (Intermediate O; 853.6 mg, 5.79 mmol) in THF (5 mL) was added a solution of n-BuLi (2.5M in hexane, 1.8 mL, 4.5 mmol). The reaction mixture was allowed to warm to −20° C. over the period of 1 h. After cooling down to −65° C. again, a solution of (±)-(4R*,5R*)-5-formyl-1-methyl-4-phenylpyrrolidin-2-one (Intermediate Z, 6.38 mmol) in THF (5 mL) was added. The reaction mixture was stirred for 1 h, while allowing to warm to −20° C., then treated with a saturated NH4Cl solution (15 mL). The resulting mixture was extracted with EtOAc (4×15 mL), dried (MgSO4) and concentrated under reduced pressure. The crude brown solid was triturated (Et2O/hex) to give (±)-(4R*,5R*)-5-{(1S*) [5-(4-fluorophenyl)(2-thienyl)]hydroxymethyl}-1-methyl-4-phenylpyrrolidin-2-one (330 mg, 24%) as a fine brown solid: mp 110° C. (dec); TLC (EtOAc) Rf 0.52.
後処理
- temperatureAfter cooling down to −65° C. again
- temperatureto warm to −20° C.
- extractionThe resulting mixture was extracted with EtOAc (4×15 mL)
- dry with materialdried (MgSO4)
- concentrationconcentrated under reduced pressure
- customThe crude brown solid was triturated (Et2O/hex)
出典と根拠
- ORDレコード
- ord-38a34247072d4ad9b7d6c6bd377c3852
- 出典データセット
- uspto-grants-2004_08
- 特許番号
- US06784167B2
反応ノート
読み込み中…