Methyl iodide → HCID 12150667, compound

HRID 2086148Notes

Reaction equation

HRID 2086148 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[C:12]([Cl:15])[C:11]([O:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([CH:25]([CH3:27])[CH3:26])[CH:18]=1)=[C:10]([Cl:28])[CH:9]=2)=[O:5])C.[H-].[Na+].I[CH3:32]>CN(C)C=O>[CH3:1][O:3][C:4]([C:6]1[N:7]([CH3:32])[C:8]2[C:13]([CH:14]=1)=[C:12]([Cl:15])[C:11]([O:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([CH:25]([CH3:26])[CH3:27])[CH:18]=1)=[C:10]([Cl:28])[CH:9]=2)=[O:5]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 12150666HCID 12150666, compound

Product 1

HCID 12150667HCID 12150667, compoundYield 90.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4,6-dichloro-5-(3-isopropyl-4-methoxy-phenoxy)-1H-indole-2-carboxylic acid ethyl ester (50 mg, 0.12 mmol) in N,N-dimethylformamide (1 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil, 4.3 mg, 0.18 mmol) and the mixture was stirred at 0° C. for 30 minutes. To which at 0° C. was added iodomethane (15 μL, 0.24 mmol). The solution was warmed to room temperature, stirred for 19 hours, quenched with 1M hydrochloric acid (15 mL) and extracted with ethyl acetate (15 mL). The organic extract was washed with 1M hydrochloric acid (4 times 20 mL), brine (20 mL), dried (Na2SO4), filtered, and concentrated. The residue was purified by preparative thin layer chromatography (50% CH2Cl2 in hexane) to afford the title compound (46 mg). 1H NMR (400 MHz, CDCl3) δ7.42 (s, 1H), 7.33 (s, 1H), 6.85 (d, 1H), 6.65 (d, 1H), 6.42-6.39 (dd, 1H), 4.05 (s, 3H), 3.91 (s, 3H), 3.91 (s, 3H), 3.74 (s, 3H), 3.27-3.23 (m, 1H), 1.15 (d, 6H).

Workup

  1. temperatureThe solution was warmed to room temperature
  2. stirringstirred for 19 hours
  3. customquenched with 1M hydrochloric acid (15 mL)
  4. extractionextracted with ethyl acetate (15 mL)
  5. extractionThe organic extract
  6. washwas washed with 1M hydrochloric acid (4 times 20 mL), brine (20 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by preparative thin layer chromatography (50% CH2Cl2 in hexane)

Sources & evidence

ORD record
ord-7d2713ae590145d880b63ef76247d7c6
Source dataset
uspto-grants-2004_04
Patent number
US06723744B2

Reaction notes

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