Methyl iodide → 1-Acetyl-6-bromo-5-fluoro-2,2-dimethylindolin-3-one

HRID 331051노트

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HRID 331051 반응식
[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([F:14])=[C:10]([Br:13])[CH:11]=2)[C:6](=[O:15])[CH:5]1[CH3:16])(=[O:3])[CH3:2].[H-].[Na+].I[CH3:20]>C1COCC1>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([F:14])=[C:10]([Br:13])[CH:11]=2)[C:6](=[O:15])[C:5]1([CH3:20])[CH3:16])(=[O:3])[CH3:2]

참가 물질

5

반응물 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 710896491-Acetyl-6-bromo-5-fluoro-2-methylindolin-3-one

생성물 1

HCID 710896451-Acetyl-6-bromo-5-fluoro-2,2-dimethylindolin-3-one수율 35.7%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a stirred mixture of 1-acetyl-6-bromo-5-fluoro-2-methylindolin-3-one (D88) (800 mg, 2.80 mmol) in THF (20 mL) at 0° C. was added sodium hydride (224 mg, 5.59 mmol). After stirring for 10 min, iodomethane (0.210 mL, 3.36 mmol) was added to the mixture. The mixture was allowed to warm to RT. The mixture was stirred for 1 hour at RT. The reaction was quenched with addition with saturated NH4Cl aq. and the mixture was poured into water (100 mL). The mixture was extracted with ethyl acetate (30 mL×3). The organic layers were combined, washed with brine (100 mL), dried over MgSO4, filtered and evaporated in vacuo. The crude residue was purified by chromatography on silica, eluting with a gradient of 0-30% ethyl acetate in cyclohexane to give title compound (300 mg). LCMS (A): m/z (M+H)+ 300/302, C12H11BrFNO2 requires 299/301 (acidic).

후처리

  1. stirringThe mixture was stirred for 1 hour at RT
  2. customThe reaction was quenched with addition with saturated NH4Cl aq.
  3. additionthe mixture was poured into water (100 mL)
  4. extractionThe mixture was extracted with ethyl acetate (30 mL×3)
  5. washwashed with brine (100 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe crude residue was purified by chromatography on silica
  10. washeluting with a gradient of 0-30% ethyl acetate in cyclohexane

출처 및 근거

ORD 기록
ord-321415bcbe764ada95c0b27921d1c3ec
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877742B2

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