Acetic Anhydride → 1-acetyl-6-bromo-5-fluoro-2-methyl-1H-indol-3-yl acetate
Reaction equation
[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]Participants
4
Conditions
- Temperature
- 150 °C
Procedure
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).
Workup
- customThe mixture was evaporated in vacuo
- additionThe residue was diluted with DCM
- additionpoured into saturated NaHCO3 aq. (200 mL)
- extractionThe mixture extracted with DCM (30 mL×3)
- washwashed with brine (100 mL)
- filtrationfiltered through phase separator
- customevaporated in vacuo
- customThe crude residue was purified by chromatography on silica
- washeluting with a gradient of 0-35% ethyl acetate in cyclohexane
Sources & evidence
- ORD record
- ord-17fef86cbc2f48f893b43009367da79d
- Source dataset
- uspto-grants-2014_11
- Patent number
- US08877742B2
Reaction notes
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