Triethylamine → 3-((3R,4R)-4-(4-(benzyloxy)phenyl)-3-hydroxypiperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one
反応式
Br[CH:2]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[C:3]1=[O:15].Cl.[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([C@H:31]2[CH2:36][CH2:35][NH:34][CH2:33][C@@H:32]2[OH:37])=[CH:27][CH:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(N(CC)CC)C>O>[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([C@H:31]2[CH2:36][CH2:35][N:34]([CH:2]3[CH2:6][CH2:5][N:4]([CH2:7][C:8]4[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=4)[C:3]3=[O:15])[CH2:33][C@@H:32]2[OH:37])=[CH:27][CH:26]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1参加物
反応物 3
生成物 1
試薬・触媒・溶媒 1
反応条件
- 温度
- 120 °C
実験手順
A mixture of 3-bromo-1-(4-methylbenzyl)pyrrolidin-2-one (Intermediate 2, 220 mg, 0.82 mmol), (3R,4R)-4-(4-(benzyloxy)phenyl)piperidin-3-ol hydrochloride (262 mg, 0.82 mmol, from step G) and triethylamine (11 mL, 8.2 mmol) was stirred at 60° C. for 1 h, 80° C. for 1 h, 100° C. for 1 h and 120° C. for 1 h. The reaction mixture was then allowed to cool, diluted with 40 mL of water and extracted four times with 50 mL of chloroform. The combined organic layers were washed with 60 mL brine, dried over anhydrous sodium sulfate, filtered, and evaporated to yield 382 mg of 3-((3R,4R)-4-(4-(benzyloxy)phenyl)-3-hydroxypiperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one which was used without further purification. LCMS (method J) (main component of a mixture) RT 2.23 min, m/z 471 (M+H+).
後処理
- temperatureto cool
- extractionextracted four times with 50 mL of chloroform
- washThe combined organic layers were washed with 60 mL brine
- dry with materialdried over anhydrous sodium sulfate
- filtrationfiltered
- customevaporated
出典と根拠
- ORDレコード
- ord-e523a126e4e04ba293f174df46fbfe81
- 出典データセット
- uspto-grants-2015_12
- 特許番号
- US09221796B2
反応ノート
読み込み中…