Methyl iodide → Methyl 2-(1-methyl-1H-indol-3-yl)acetate

HRID 2376216Notes

Reaction equation

HRID 2376216 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:16])[CH2:6][C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[NH:9][CH:8]=1.[CH3:17]I>CN(C=O)C>[CH3:3][O:4][C:5](=[O:16])[CH2:6][C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]([CH3:17])[CH:8]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 74706Methyl indole-3-acetate

Product 1

HCID 11106438Methyl 2-(1-methyl-1H-indol-3-yl)acetateYield 19%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of sodium hydride (104 mg, 7.61 mmol) in DMF (11 mL) was added a solution of 1H-indol-3-yl-acetic acid methyl ester (0.50 g, 2.6 mmol) in DMF (5.0 mL). The mixture was stirred for 1 h followed by addition of methyl iodide (1.1 g, 7.8 mmol). The reaction mixture was stirred for an additional 18 h, quenched, diluted with saturated ammonium chloride (200 mL), and then extracted with diethyl ether (3×100 mL). The combined organic layers were dried with Na2SO4, and the solvent was removed under reduced pressure. The crude residue was purified by flash chromatography (EtOAc/hexanes) giving 100 mg (19%) of (1-methyl-1H-indol-3-yl)-acetic acid methyl ester after purification. HPLC: Rt=8.91 (Method A). MS (ES+): mass calculated for C12H13NO2, 203.09; m/z found 204.09 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.60 (d, J=7.9 Hz, 1H), 7.30 (d, J=8.2 Hz, 1H), 7.23 (t, J=8.2 Hz, 1H), 7.13 (t, 7.4 Hz, 1H), 7.04 (s, 1H), 3.77 (s, 2H), 3.76 (s, 3H), 3.69 (s, 3H).

Workup

  1. stirringThe reaction mixture was stirred for an additional 18 h
  2. customquenched
  3. additiondiluted with saturated ammonium chloride (200 mL)
  4. extractionextracted with diethyl ether (3×100 mL)
  5. dry with materialThe combined organic layers were dried with Na2SO4
  6. customthe solvent was removed under reduced pressure
  7. customThe crude residue was purified by flash chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-ce41acd736de430683afc3cb2b85d841
Source dataset
uspto-grants-2008_12
Patent number
US07465808B2

Reaction notes

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