Water ethylacetate → (4R)-4-(2-bromo-4-chlorophenyl)pyrrolidin-2-one

HRID 1799185ノート

反応式

HRID 1799185 の反応式
N[C:2]1[CH:3]=[C:4]([C@@H:10]2[CH2:14][NH:13][C:12](=[O:15])[CH2:11]2)[C:5]([Br:9])=[CH:6][C:7]=1[Cl:8].C(OCC)(=O)C.O.N([O-])=O.[Na+]>S(=O)(=O)(O)O>[Br:9][C:5]1[CH:6]=[C:7]([Cl:8])[CH:2]=[CH:3][C:4]=1[C@@H:10]1[CH2:14][NH:13][C:12](=[O:15])[CH2:11]1

参加物

5

反応物 3

HCID 22728543Water ethylacetateHCID 23668193Sodium NitriteHCID 66724936(4R)-4-(3-Amino-6-bromo-4-chlorophenyl)pyrrolidin-2-one

生成物 1

HCID 66725008(4R)-4-(2-bromo-4-chlorophenyl)pyrrolidin-2-one収率 55%

試薬・触媒・溶媒 1

HCID 1118Sulfuric Acid溶媒

反応条件

温度
55 °C

実験手順

(4R)-4-(3-Amino-6-bromo-4-chlorophenyl)pyrrolidin-2-one was dissolved in 32 mL of sulfuric acid aqueous solution (1M) and the heated at 55° C. for 20 min. The reaction mixture was cooled to 0° C. and 160 mL ethyl acetate/water added. To this mixture, 1.5 equivalent of NaNO2 was added portion wise. The reaction was monitored by LCMS. After the starting material was consumed, the mixture was diluted with water and extracted with dichloromethane. The combined organic phases were washed with water and brine, and dried over sodium sulfate. The solvent was removed to provide the title compound as an off-white solid (4.7 g, 55% yield). 1H-NMR (400 MHz, CD3OD): δ 2.38-2.44 (dd, J=17.2, 4.0 Hz, 1H), 2.73-2.80 (dd, J=17.2, 9.2 Hz, 1H), 3.33-3.37 (dd, J=10.0, 6 Hz, 5.6 Hz, 1H), 3.78-3.83 (dd, J=10.0, 8.0 Hz, 1H), 4.06-4.13 (m, 1H), 7.64-7.65 (m, 1H), 7.38 (m, 2H); MS (ESI) m/z 275.89 (M+H)+.

後処理

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. customAfter the starting material was consumed
  3. additionthe mixture was diluted with water
  4. extractionextracted with dichloromethane
  5. washThe combined organic phases were washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was removed

出典と根拠

ORDレコード
ord-3f739c79cc3d4340879203e37a9bddfb
出典データセット
uspto-grants-2013_01
特許番号
US08344028B2

反応ノート

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