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Sodium hydride → (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)piperidin-2-one

HRID 931916
ノート
印刷プレビュー

反応式

HRID 931916 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[NH:12][C:11](=[O:21])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[CH:24]1([CH2:27]Br)[CH2:26][CH2:25]1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)[N:12]([CH2:27][CH:24]3[CH2:26][CH2:25]3)[C:11](=[O:21])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 58573791(5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one

生成物 1

HCID 60154112(5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)piperidin-2-one

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

To a solution of 1.5 g (4.7 mmol) of (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one (Example 1, Step E) in 9.4 mL of DMF was added sodium hydride (60% suspension in mineral oil, 244 mg, 6.1 mmol) at 0° C. The reaction was stirred at 0° C. for 20 min and then treated with cyclopropylmethyl bromide (759 μl, 5621 μmol). After being stirred at 25° C. for 5 h, the reaction was quenched (sat. aqueous NH4Cl), extracted (2×EtOAc). The combined organic layers were washed with sat. aq. NaCl and NaHCO3— solutions, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Purification of the residue by flash chromatography on silica gel (30 to 50% EtOAc/hexanes, gradient elution) provided the title compound as a colorless foam.

後処理

  1. stirringAfter being stirred at 25° C. for 5 h
  2. customthe reaction was quenched (sat. aqueous NH4Cl)
  3. extractionextracted (2×EtOAc)
  4. washThe combined organic layers were washed with sat. aq. NaCl and NaHCO3— solutions
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customPurification of the residue by flash chromatography on silica gel (30 to 50% EtOAc/hexanes, gradient elution)

出典と根拠

ORDレコード
ord-e834bca6a9bb43a28f03dbab4431415a
出典データセット
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09296736B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート