Acetic Anhydride → 1-acetyl-6-bromo-5-fluoro-2-methyl-1H-indol-3-yl acetate

HRID 331049ノート

反応式

HRID 331049 の反応式
[Br:1][C:2]1[C:10]([F:11])=[CH:9][C:5](C(O)=O)=[C:4]([NH:12][CH:13]([C:15]([OH:17])=O)[CH3:14])[CH:3]=1.[C:18]([O-:21])(=O)[CH3:19].[Na+].[C:23](OC(=O)C)(=[O:25])[CH3:24]>>[C:23]([O:17][C:15]1[C:5]2[C:4](=[CH:3][C:2]([Br:1])=[C:10]([F:11])[CH:9]=2)[N:12]([C:18](=[O:21])[CH3:19])[C:13]=1[CH3:14])(=[O:25])[CH3:24]

参加物

4

反応物 3

HCID 7918Acetic AnhydrideHCID 517045Sodium AcetateHCID 710896524-Bromo-2-((1-carboxyethyl)amino)-5-fluorobenzoic acid

生成物 1

HCID 710904071-acetyl-6-bromo-5-fluoro-2-methyl-1H-indol-3-yl acetate収率 72%

反応条件

温度
150 °C

実験手順

A mixture of 4-bromo-2-((1-carboxyethyl)amino)-5-fluorobenzoic acid (D86) (1.599 g, 5.22 mmol), sodium acetate (1.714 g, 20.90 mmol) and acetic anhydride (19.72 mL, 209 mmol) was heated at 150° C. for 30 min in a microwave. The mixture was evaporated in vacuo. The residue was diluted with DCM and poured into saturated NaHCO3 aq. (200 mL). The mixture extracted with DCM (30 mL×3). The organic layers were combined, washed with brine (100 mL), filtered through phase separator and evaporated in vacuo. The crude residue was purified by chromatography on silica, eluting with a gradient of 0-35% ethyl acetate in cyclohexane to give title compound (1.233 g). LCMS (A): m/z (M+H)+ 328/330, C13H11BrFNO3 requires 327/329 (acidic).

後処理

  1. customThe mixture was evaporated in vacuo
  2. additionThe residue was diluted with DCM
  3. additionpoured into saturated NaHCO3 aq. (200 mL)
  4. extractionThe mixture extracted with DCM (30 mL×3)
  5. washwashed with brine (100 mL)
  6. filtrationfiltered through phase separator
  7. customevaporated in vacuo
  8. customThe crude residue was purified by chromatography on silica
  9. washeluting with a gradient of 0-35% ethyl acetate in cyclohexane

出典と根拠

ORDレコード
ord-17fef86cbc2f48f893b43009367da79d
出典データセット
uspto-grants-2014_11
特許番号
US08877742B2

反応ノート

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