Sodium hydride → HCID 66899007, compound

HRID 2168545Notes

Reaction equation

HRID 2168545 reaction equation
[NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([C:10]([O:12][CH3:13])=[O:11])[C:4]=2[CH:3]=[CH:2]1.[H-].[Na+].[CH3:16][O:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Br)=[CH:20][CH:19]=1>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:16][O:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][N:1]2[C:9]3[CH:8]=[CH:7][CH:6]=[C:5]([C:10]([O:12][CH3:13])=[O:11])[C:4]=3[CH:3]=[CH:2]2)=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 1650214-Methoxybenzyl bromideHCID 2733668methyl 1H-indole-4-carboxylate

Product 1

HCID 66899007HCID 66899007, compoundYield 98.4%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl indole-4-carboxylate (10.0 g, 57.1 mmol) was added sodium hydride (60% dispersion in mineral oil (5.7 g, 142.8 mmol) in DMF (200 mL) at 0° C. The mixture was stirred under an atmosphere of nitrogen for 15 min. To this were added 4-methoxybenzyl bromide (10.7 g, 68.5 mmol) and tetrabuylammonium iodide (3.2 g, 8.6 mmol). The resulting mixture continued to stir for 10 min and then warmed to room temperature and stirred for 2.5 h. The mixture was quenched with sat. aqueous ammonium chloride (200 mL) and extracted with diethyl ether (3×500 mL). The combined organic layers were washed with brine (3×200 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The crude material was purified by column chromatography (silica gel, 5 to 20% ethyl acetate in hexanes), providing methyl 1-(4-methoxybenzyl)-1H-indole-4-carboxylate (16.6 g, 98%) as a pale yellow oil: 1H NMR δ (500 MHz, CDCl3) 7.90 (d, J=10.0 Hz, 1H), 7.49 (d, J=1.0 Hz, 1H), 7.26-7.25 (m, 1H), 7.20 (t, J=10.0 Hz, 1H), 7.16-7.15 (m, 1H), 7.04 (d, J=10.0 Hz, 2H), 6.82 (d, J=10.0 Hz, 2H), 5.29 (s, 2H), 3.98 (s, 3H), 3.77 (s, 3H); MS (ESI+) m/z 296 (M+H).

Workup

  1. stirringto stir for 10 min
  2. stirringstirred for 2.5 h
  3. customThe mixture was quenched with sat. aqueous ammonium chloride (200 mL)
  4. extractionextracted with diethyl ether (3×500 mL)
  5. washThe combined organic layers were washed with brine (3×200 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by column chromatography (silica gel, 5 to 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-b5cba7044ddf4deaa9775972cc30760f
Source dataset
uspto-grants-2015_06
Patent number
US09045501B2

Reaction notes

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