1,3-Dibromopropane → methyl [5-(3-bromopropoxy)-1H-indol-1-yl]acetate

HRID 734416Notes

Reaction equation

HRID 734416 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH:6]=[CH:5]2.[Br:16][CH2:17][CH2:18][CH2:19]Br.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[Br:16][CH2:17][CH2:18][CH2:19][O:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH:6]=[CH:5]2

Participants

5

Reactant 3

HCID 80011,3-DibromopropaneHCID 10796Cesium carbonateHCID 20770839methyl (5-hydroxy-1H-indol-1-yl)acetate

Product 1

HCID 57845410methyl [5-(3-bromopropoxy)-1H-indol-1-yl]acetateYield 45.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl (5-hydroxy-1H-indol-1-yl)acetate (1.0 g, 4.87 mmol) (Example 9) in 35 mL DMF, was added 1,3-dibromopropane (5.90 g, 29.24 mmol) and Cs2CO3 (3.18 g, 9.75 mmol). The mixture was stirred at rt for 6 h, and then the solvent was evaporated under reduced pressure. The residue was suspended in EtOAc, filtered, and the filter cake was washed with EtOAc. The combined organic layers were dried, concentrated, and purified by column chromatography (0-10% EtOAc in hexane) to give 720 mg (45%) of the product containing minor impurities. This material was used in later steps with no further purification. 1H NMR (400 MHz, CDCl3) δ 7.18-7.10 (m, 2H), 7.05 (d, 1H), 6.94-6.85 (m, 1H), 6.50 (d, 1H), 4.80 (s, 2H), 4.18 (t, 2H), 3.75 (s, 3H), 3.65 (t, 2H), 2.40-2.30 (m, 2H).

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. filtrationfiltered
  3. washthe filter cake was washed with EtOAc
  4. customThe combined organic layers were dried
  5. concentrationconcentrated
  6. custompurified by column chromatography (0-10% EtOAc in hexane)

Sources & evidence

ORD record
ord-f38cd97c9a1349e682d80d2b7e681e39
Source dataset
uspto-grants-2009_09
Patent number
US07592361B2

Reaction notes

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