Hydrochloric Acid → Methyl 3-methoxy-4-((1-methyl-5-nitro-1H-indol-3-yl)methyl)benzoate

HRID 275122Notes

Reaction equation

HRID 275122 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([N+:23]([O-:25])=[O:24])[CH:21]=2)[NH:16][CH:15]=1)[C:6]([O:8][CH3:9])=[O:7].[H-].[Na+].I[CH3:29].Cl>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([N+:23]([O-:25])=[O:24])[CH:21]=2)[N:16]([CH3:29])[CH:15]=1)[C:6]([O:8][CH3:9])=[O:7]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 114732633-(2-Methoxy-4-methoxycarboxybenzyl)-5-nitroindole

Product 1

HCID 11772604Methyl 3-methoxy-4-((1-methyl-5-nitro-1H-indol-3-yl)methyl)benzoateYield 73.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methyl 3-methoxy-4-(5-nitroindol-3-ylmethyl)benzoate (C) (0.44 g.) was added to a stirred suspension of oil-free sodium hydride (0.031 g.) in dry tetrahydrofuran (10 ml.), under an atmosphere of nitrogen. The dark-red solution was stirred for 10 minutes, and iodomethane (0.18 g.) was added. The mixture was stirred for 30 minutes, and was poured into 1M hydrochloric acid (30 ml.). The mixture obtained was extracted with ethyl acetate (2×50 ml.). The combined extracts were washed with brine (25 ml.), then dried (MgSO4), and evaporated. The yellow oil obtained was purified by flash chromatography on silica gel (50 ml.), eluting with 50:45:5 v/v/v hexane:dichloromethane:ethyl acetate, to give methyl 3-methoxy-4-(1-methyl-5-nitroindol-3-ylmethyl)benzoate (E) (0.33 g., 72%) as a yellow oil, which was crystallized from dichloromethane/hexane to give a yellow solid, m.p. 144°-146° C.; NMR: 3.81(s,3H, N.CH3), 3.83(s,3H, CO.OCH3), 3.92(s,3H, OCH3), 4.11(s,2H, CH2.Ar), 7.27(d,1H), 7.37(s,1H, H2 -indole), 7.49(m,2H), 7.60(d,1H), 8.01(dd,1H, H6 -indole), 8.50(d,1H, H4 -indole).

Workup

  1. stirringThe mixture was stirred for 30 minutes
  2. customThe mixture obtained
  3. extractionwas extracted with ethyl acetate (2×50 ml.)
  4. washThe combined extracts were washed with brine (25 ml.)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe yellow oil obtained
  8. customwas purified by flash chromatography on silica gel (50 ml.)
  9. washeluting with 50:45:5 v/v/v hexane

Sources & evidence

ORD record
ord-58c750a17751453a81872eb663b4de26
Source dataset
uspto-grants-1995_02
Patent number
US05391758

Reaction notes

Loading…