Water → 3-((3S,4S)-3-fluoro-4-(4-hydroxy-phenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one

HRID 1507223ノート

反応式

HRID 1507223 の反応式
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].C(N(CC)CC)C.Cl.[F:24][C@H:25]1[C@H:30]([C:31]2[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=2)[CH2:29][CH2:28][NH:27][CH2:26]1.O>CN(C=O)C>[F:24][C@H:25]1[C@H:30]([C:31]2[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=2)[CH2:29][CH2:28][N:27]([CH:2]2[CH2:6][CH2:5][N:4]([CH2:7][C:8]3[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=3)[C:3]2=[O:15])[CH2:26]1

参加物

6

反応物 4

HCID 962WaterHCID 8471TriethylamineHCID 637890883-Bromo-1-(4-methylbenzyl)pyrrolidin-2-oneHCID 1182073504-((3S,4S)-3-fluoropiperidin-4-yl)phenol hydrochloride

生成物 1

HCID 1182073253-((3S,4S)-3-fluoro-4-(4-hydroxy-phenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one収率 92.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
120 °C

実験手順

A mixture of 3-bromo-1-(4-methylbenzyl)pyrrolidin-2-one (200 mg, 0.75 mmol), triethylamine (0.52 mL, 3.7 mmol) and 4-((3S,4S)-3-fluoropiperidin-4-yl)phenol hydrochloride (173 mg, 0.75 mmol) in DMF (3 mL) was heated to 120° C. in a microwave reactor for 1.5 h. The mixture was allowed to cool and was then mixed with 60 mL water and extracted 5 times with 40 mL of DCM. The combined organic extracts were washed with 80 mL of brine, dried over anhydrous sodium sulfate, filtered, and evaporated to give 265 mg of 3-((3S,4S)-3-fluoro-4-(4-hydroxy-phenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one as a mixture of 2 diastereoisomers. LCMS (method P) RT 0.92 min m/z 383.4 (M+H+).

後処理

  1. temperatureto cool
  2. extractionextracted 5 times with 40 mL of DCM
  3. washThe combined organic extracts were washed with 80 mL of brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customevaporated

出典と根拠

ORDレコード
ord-cc4e422416b94d3b94092ee336d24a1a
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…