Methyl iodide → Methyl 4-(5-benzyloxycarbonyl-1-methylindol-3-ylmethyl)-3-methoxybenzoate

HRID 1975417Notes

Reaction equation

HRID 1975417 reaction equation
[CH2:1]([O:8][C:9]([C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH:15]=[C:14]2[CH2:20][C:21]1[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][C:22]=1[O:31][CH3:32])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:36]>CN(C)C=O.O.Cl>[CH2:1]([O:8][C:9]([C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH3:36])[CH:15]=[C:14]2[CH2:20][C:21]1[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][C:22]=1[O:31][CH3:32])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 10252039HCID 10252039, compound

Product 1

HCID 10343359Methyl 4-(5-benzyloxycarbonyl-1-methylindol-3-ylmethyl)-3-methoxybenzoateYield 89.1%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
5 °C

Procedure

A solution of methyl 4-(5-benzyloxycarbonylindol-3-ylmethyl)-3-methoxybenzoate (46.1 g) in N,N-dimethylformamide (200 mL) was added to a slurry of sodium hydride (2.83 g) in N,N-dimethylformamide (300 mL) at 5° C. under a nitrogen atmosphere. The mixture was stirred for 30 minutes at 5° C., then was treated with iodomethane (16.6 g), allowed to warm to room temperature and stirred for 16 hours. The reaction mixture was then poured into ice/water (400 mL), diluted with water (250 mL) and 1N hydrochloric acid (250 mL). The resulting aqueous solution was extracted with ethyl acetate. The combined organic extract was washed (1N hydrochloric acid, water, brine), dried (MgSO4), filtered and evaporated. The residue was triturated with warm diethyl ether and filtered to give methyl 4-(5-benzyloxycarbonyl-1-methylindol-3-ylmethyl)-3-methoxybenzoate as an ivory solid (42.4 g, 89%); partial NMR (300 MHz, CDCl3): 3.75 (s, 3H, NCH3), 3.87 (s, 3H, CO2CH3), 3.90 (s, 3H, OCH3), 4.12 (s, 2H, CH2), 5.36 (s, 2H, OCH2), 6.82 (s, 1H, indole-H(2)), 8.38 (d, 1H, indole-H(4)).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 16 hours
  3. extractionThe resulting aqueous solution was extracted with ethyl acetate
  4. extractionThe combined organic extract
  5. washwas washed (1N hydrochloric acid, water, brine)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was triturated with warm diethyl ether
  10. filtrationfiltered

Sources & evidence

ORD record
ord-1ba73776333e4a82ab5523697a467bd3
Source dataset
uspto-grants-1994_02
Patent number
US05286740

Reaction notes

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