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

HRID 2424960Notes

Reaction equation

HRID 2424960 reaction equation
[CH3:1][O:2][C:3](=[O:15])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([OH:14])=[CH:11][CH:12]=2)[CH:7]=[CH:6]1.[Br:16][CH2:17][CH2:18][CH2:19]Br.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:15])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH2:19][CH2:18][CH2:17][Br:16])=[CH:11][CH:12]=2)[CH:7]=[CH:6]1

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-ec9e6577aaf84e4bb82ccf26188dbe1e
Source dataset
uspto-grants-2011_06
Patent number
US07964622B2

Reaction notes

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