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

HRID 1799185노트

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HRID 1799185 반응식
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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 1118Sulfuric Acid용매

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온도
55 °C

실험 절차

(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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-3f739c79cc3d4340879203e37a9bddfb
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08344028B2

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