Sodium hydride → Methyl 2-(6-bromo-5-fluoro-1H-indol-1-yl)acetate

HRID 331043Notes

Reaction equation

HRID 331043 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][C:3]=1[F:11].[H-].[Na+].Br[CH2:15][C:16]([O:18][CH3:19])=[O:17]>CN(C=O)C>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[CH2:15][C:16]([O:18][CH3:19])=[O:17])=[CH:4][C:3]=1[F:11]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 222629226-Bromo-5-fluoroindole

Product 1

HCID 71090281Methyl 2-(6-bromo-5-fluoro-1H-indol-1-yl)acetateYield 76.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-Bromo-5-fluoro-1H-indole (10 g, 46.7 mmol) was dissolved in DMF (100 mL) and cooled to 0° C. in an ice bath before the addition of sodium hydride, 60% dispersion in mineral oil (3.74 g, 93 mmol) and methyl 2-bromoacetate (8.59 mL, 93 mmol). The ice bath was removed and the reaction mixture was stirred at RT for 1 hour. The reaction mixture was cooled with an ice bath once again then quenched with water (50 mL). The aqueous layer was extracted with DCM (3×200 mL). The organics were combined, passed through a hydrophobic frit and concentrated. The residue was purified by column chromatography on silica gel, eluting with a gradient of 0-40% ethyl acetate in cyclohexane to afford the title compound (10.209 g). LCMS (A): m/z (M+H)+ 286/288, C11H9BrFNO2 requires 285/287 (acidic).

Workup

  1. customThe ice bath was removed
  2. temperatureThe reaction mixture was cooled with an ice bath once again
  3. customquenched with water (50 mL)
  4. extractionThe aqueous layer was extracted with DCM (3×200 mL)
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel
  7. washeluting with a gradient of 0-40% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-b6c489bf27d548acb8f457ae9bf32ad9
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

Loading…