Hydrochloric Acid → Methyl 4-(5-formyl-1-methylindol-3-ylmethyl)-3-methoxybenzoate

HRID 728043Notes

Reaction equation

HRID 728043 reaction equation
[H-].[Na+].[CH:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[C:8]2[CH2:14][C:15]1[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][C:16]=1[O:25][CH3:26])=[O:4].[CH3:27]I.Cl>CN(C)C=O>[CH:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH3:27])[CH:9]=[C:8]2[CH2:14][C:15]1[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][C:16]=1[O:25][CH3:26])=[O:4]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 14882554Methyl 4-(5-formylindol-3-ylmethyl)-3-methoxybenzoate

Product 1

HCID 14882555Methyl 4-(5-formyl-1-methylindol-3-ylmethyl)-3-methoxybenzoateYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (1.23 g of a 60% dispersion in mineral oil) was added to dry N,N-dimethylformamide (100 ml), under an atmosphere of nitrogen. The mixture was cooled in an ice-bath, a solution of methyl 4-(5-formylindol-3-ylmethyl)-3-methoxybenzoate (9.0 g) in N,N-dimethylformamide (20 ml) added slowly, and the mixture stirred for 1 hr. Methyl iodide (4.34 g) was added slowly, stirring continued for 2.5 hr., then the mixture carefully acidified with hydrochloric acid (100 ml) to give an off-white precipitate which was purified by flash chromatography, eluting with 45:50:5 hexane:methylene chloride:ethyl acetate, to give a yellow oil which was crystallized from a mixture of ethyl acetate and hexane to give methyl 4-(5-formyl-1-methylindol-3-ylmethyl)-3-methoxybenzoate (81%) as an off-white powder; mp 116-118 C°; partial NMR(250 MHz, DMSO-d6): 3.80 (s, 3H, OCH3), 3.83(s, 3H, NCH3), 3.93(s, 3H, OCH3), 4.11(s, 2H, ArCH2Ar'), 8.12(s, lH, H4-indole), 9.96 (s, 1H, CHO).

Workup

  1. temperatureThe mixture was cooled in an ice-bath
  2. stirringstirring
  3. waitcontinued for 2.5 hr
  4. customto give an off-white precipitate which
  5. customwas purified by flash chromatography
  6. washeluting with 45:50:5 hexane
  7. custommethylene chloride:ethyl acetate, to give a yellow oil which
  8. customwas crystallized from a mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-473512d60a714f3f9c19a22e595c001f
Source dataset
uspto-grants-1991_09
Patent number
US05047402

Reaction notes

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