Methyl iodide → {2-[3-(2-fluoro-benzenesulfonyl)-1-methyl-1H-indol-7-yloxy]-ethyl}-methyl-carbamic acid tert-butyl ester

HRID 6951Notes

Reaction equation

HRID 6951 reaction equation
[C:1]([O:5][C:6](=[O:31])[N:7]([CH2:9][CH2:10][O:11][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:20]=1[NH:19][CH:18]=[C:17]2[S:21]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[F:30])(=[O:23])=[O:22])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:34]I>CN(C)C=O>[C:1]([O:5][C:6](=[O:31])[N:7]([CH2:9][CH2:10][O:11][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:20]=1[N:19]([CH3:34])[CH:18]=[C:17]2[S:21]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[F:30])(=[O:23])=[O:22])[CH3:8])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 23544637{2-[3-(2-fluoro-benzenesulfonyl)-1H-indol-7-yloxy]-ethyl}-methyl-carbamic acid tert-butyl ester

Product 1

HCID 23544633{2-[3-(2-fluoro-benzenesulfonyl)-1-methyl-1H-indol-7-yloxy]-ethyl}-methyl-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A dry 25 mL flask equipped with a magnetic stirrer was charged with {2-[3-(2-fluoro-benzenesulfonyl)-1H-indol-7-yloxy]-ethyl}-methyl-carbamic acid tert-butyl ester (0.116 g., 0.258 mmol) and dimethylformamide (5 mL.) This solution was treated with sodium hydride (0.011 g. of 60% suspension in mineral oil, 0.284 mmol) and allowed to stir for 10 minutes under N2. Methyl iodide was then added via syringe in one portion. After 18 hours stirring at ambient temperature, the reaction mixture was extracted into 45 mL ethyl acetate and washed with water (2×45 mL). The organic fraction was dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (85:15 hexanes:EtOAc to 70:30 hexanes:EtOAc) to give 45 mg of {2-[3-(2-fluoro-benzenesulfonyl)-1-methyl-1H-indol-7-yloxy]-ethyl}-methyl -carbamic acid tert-butyl ester as a clear oil: 1H NMR (CDCl3, 300 MHz) δ: 1.45 (s, 9H), 2.94 (s, 3H), 3.71 (m, 2H), 4.09 (s, 3H), 4.19 (m, 2H), 6.67 (d, 1H, J=7.7), 7.04 (m, 1H), 7.08 (t, 1H, J=8.0), 7.27 (td, 1H, J=7.6, J′=1.13), 7.44 (d, 1H, J=7.6), 7.49 (m, 1H), 7.74 (d, 1H, J=1.3), 8.15 (td, 1H, J=7.6, J′=1.8).

Workup

  1. customA dry 25 mL flask equipped with a magnetic stirrer
  2. stirringAfter 18 hours stirring at ambient temperature
  3. extractionthe reaction mixture was extracted into 45 mL ethyl acetate
  4. washwashed with water (2×45 mL)
  5. dry with materialThe organic fraction was dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (85:15 hexanes:EtOAc to 70:30 hexanes:EtOAc)

Sources & evidence

ORD record
ord-657f79367abc4069a1261c2d77576d05
Source dataset
uspto-grants-2006_08
Patent number
US07084169B2

Reaction notes

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