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

HRID 2248773Notes

Reaction equation

HRID 2248773 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].Br[CH2:28][CH2:29][CH3:30].Cl>CN(C)C=O>[CH:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH2:28][CH2:29][CH3:30])[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 78401-BromopropaneHCID 24758Sodium hydrideHCID 14882554Methyl 4-(5-formylindol-3-ylmethyl)-3-methoxybenzoate

Product 1

HCID 14882683Methyl 4-(5-formyl-1-propylindol-3-ylmethyl)-3-methoxybenzoateYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (2.96 g of a 60% w/w dispersion in mineral oil) was added to dry dimethylformamide (DMF, 100 ml), under a nitrogen atmosphere. The mixture was stirred and cooled in an ice-bath, and a solution of methyl 4-(5-formylindol-3-ylmethyl)-3-methoxybenzoate (20 g) in DMF (75 ml) added slowly. After 1 h, 1-bromopropane (9.13 g) was added slowly. After 2 h, the mixture was carefully acidified with 2M hydrochloric acid (100 ml), extracted with ethyl acetate (twice), and the extract washed with 1M hydrochloric acid, water, and brine. The dried (MgSO4) solution was evaporated, and the residue dissolved in ethyl acetate and filtered through a pad of silica gel. The filtrate was evaporated and the product crystallised from ether to give methyl 4-(5-formyl-1-propylindol-3-ylmethyl)-3-methoxybenzoate (19.2 g, 85%) as white needles; mp 98°-99°; partial NMR (250 MHz, DMSO-d6): 0.82 (t, 3H, CH3), 1.75 (m, 2H, CH2), 3.83 (s, 3H, OCH3), 3.92 (s, 3H, OCH3), 4.1 (m, 4H, ArCH2Ar' and NCH2), 9.95 (s, 1H, CHO).

Workup

  1. temperaturecooled in an ice-bath
  2. waitAfter 2 h
  3. extractionextracted with ethyl acetate (twice), and the extract
  4. washwashed with 1M hydrochloric acid, water, and brine
  5. dry with materialThe dried (MgSO4) solution
  6. customwas evaporated
  7. dissolutionthe residue dissolved in ethyl acetate
  8. filtrationfiltered through a pad of silica gel
  9. customThe filtrate was evaporated
  10. customthe product crystallised from ether

Sources & evidence

ORD record
ord-af5ea256192f4adca75df492b0958ab5
Source dataset
uspto-grants-1991_08
Patent number
US05041460

Reaction notes

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