Chloroacetyl chloride → 2-chloro-N-[2-(2,6-dioxo-3-piperidyl)-1-oxo-isoindolin-4-yl]acetamide

HRID 2103495

反応式

HRID 2103495 の反応式
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][N:5]([CH:12]1[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[C:6]2=[O:11].[Cl:20][CH2:21][C:22](Cl)=[O:23]>C1COCC1.ClCC(Cl)=O>[O:19]=[C:13]1[CH:12]([N:5]2[CH2:4][C:3]3[C:7](=[CH:8][CH:9]=[CH:10][C:2]=3[NH:1][C:22](=[O:23])[CH2:21][Cl:20])[C:6]2=[O:11])[CH2:17][CH2:16][C:15](=[O:18])[NH:14]1

参加物

5

反応物 2

HCID 6577Chloroacetyl chlorideHCID 216326Lenalidomide

生成物 1

HCID 98808592-chloro-N-[2-(2,6-dioxo-3-piperidyl)-1-oxo-isoindolin-4-yl]acetamide収率 92.1%

試薬・触媒・溶媒 2

HCID 6577Chloroacetyl chloride触媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a stirred suspension of 3-(4-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione (3.89 g, 15.0 mmol) in THF (50 ml) was added chloroacetyl chloride (1.86 g, 16.5 mmol). The mixture was heated to reflux for 45 minutes. To the reaction mixture was added additional chloroacetyl chloride (0.15 g, 0.13 mmol). The reaction mixture was heated at reflux for an additional 30 minutes. The solvent was evaporated in vacuo and the resulting solid was slurried in diethyl ether (20 ml) and filtered to give 4.64 g (92%) of product as an off-white solid: 1H NMR (DMSO-d6) δ 11.04 (s, 1H), 10.22 (s, 1H), 7.82 (dd, J=1.6 and 7.2 Hz, 1H), 7.59-7.50 (m, 2H), 5.16 (dd, J=5.1 and 13.2 Hz, 1H), 4.46-4.30 (m, 4H), 3.00-2.85 (m, 1H), 2.65-2.58 (m, 1H), 2.44-2.28 (m, 1H), 2.06-2.01 (m, 1H).

後処理

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 45 minutes
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux for an additional 30 minutes
  5. customThe solvent was evaporated in vacuo
  6. filtrationfiltered

出典と根拠

ORDレコード
ord-e12ce7a47c7c464c8e5e245ebca573b0
出典データセット
uspto-grants-2009_08
特許番号
US07576104B2

関連ノート

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