Potassium Iodide → {4-[3-(7-Propyl-3-trifluoromethyl-benzo[d]isoxazol-6-yloxy)-propoxy]-indol-1-yl}-acetic acid methyl ester

HRID 269957Notes

Reaction equation

HRID 269957 reaction equation
[NH:1]1[C:9]2[C:4](=[C:5]([O:10][CH2:11][CH2:12][CH2:13][O:14][C:15]3[CH:27]=[CH:26][C:18]4[C:19]([C:22]([F:25])([F:24])[F:23])=[N:20][O:21][C:17]=4[C:16]=3[CH2:28][CH2:29][CH3:30])[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[CH3:31][O:32][C:33](=[O:36])[CH2:34]Br.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(#N)C>[CH3:31][O:32][C:33](=[O:36])[CH2:34][N:1]1[C:9]2[C:4](=[C:5]([O:10][CH2:11][CH2:12][CH2:13][O:14][C:15]3[CH:27]=[CH:26][C:18]4[C:19]([C:22]([F:24])([F:23])[F:25])=[N:20][O:21][C:17]=4[C:16]=3[CH2:28][CH2:29][CH3:30])[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 60984Methyl bromoacetateHCID 115245536-[3-(1H-indol-4-yloxy)-propoxy]-7-propyl-3-trifluoromethyl-benzo[d]isoxazole

Product 1

HCID 11569417{4-[3-(7-Propyl-3-trifluoromethyl-benzo[d]isoxazol-6-yloxy)-propoxy]-indol-1-yl}-acetic acid methyl esterYield 76%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 6-[3-(1H-indol-4-yloxy)-propoxy]-7-propyl-3-trifluoromethyl-benzo[d]isoxazole (0.100 g, 0.24 mmol), methyl-2-bromoacetate (0.109 g, 0.72 mmol), potassium carbonate (0.050 g, 0.36 mmol), potassium iodide (0.008 g, 0.05 mmol), and acetonitrile (15 mL) was stirred and refluxed for 12 hours. The mixture was cooled to room temperature and filtered to remove suspended salts. The solvent was removed in vacuo and the residue partitioned between dichloromethane and water. The organic layer was collected, washed with water (2×20 mL) and brine (2×20 mL), and then dried over anhydrous Na2SO4. The solvent was removed and the residue was purified by flash chromatograph over silica gel using hexane/ethyl acetate (95/5) as an eluant to afford {4-[3-(7-propyl-3-trifluoromethyl-benzo[d]isoxazol-6-yloxy)-propoxy]-indol-1-yl}-acetic acid methyl ester (0.089 g, yield: 76%).

Workup

  1. temperaturerefluxed for 12 hours
  2. filtrationfiltered
  3. customto remove
  4. customThe solvent was removed in vacuo
  5. customthe residue partitioned between dichloromethane and water
  6. customThe organic layer was collected
  7. washwashed with water (2×20 mL) and brine (2×20 mL)
  8. dry with materialdried over anhydrous Na2SO4
  9. customThe solvent was removed
  10. customthe residue was purified by flash chromatograph over silica gel

Sources & evidence

ORD record
ord-394f7bbd21e94f00a5e6f45824a8d3ac
Source dataset
uspto-grants-2008_11
Patent number
US07449478B2

Reaction notes

Loading…