Sodium hydride → HCID 19870540, compound

HRID 330184Notes

Reaction equation

HRID 330184 reaction equation
[CH:1]([C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH2:12][CH2:13][CH3:14])=[CH:8][NH:9]2)=[CH:5][CH:4]=1)=[O:2].[H-].[Na+].Br[CH2:18][C:19]1[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][C:20]=1[O:29][CH3:30]>CN(C)C=O>[CH3:30][O:29][C:20]1[CH:21]=[C:22]([CH:27]=[CH:28][C:19]=1[CH2:18][N:9]1[C:10]2[C:6](=[CH:5][CH:4]=[C:3]([CH:1]=[O:2])[CH:11]=2)[C:7]([CH2:12][CH2:13][CH3:14])=[CH:8]1)[C:23]([O:25][CH3:26])=[O:24]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2759828Methyl 4-(bromomethyl)-3-methoxybenzoateHCID 19870622HCID 19870622, compound

Product 1

HCID 19870540HCID 19870540, compoundYield 97.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

6-Formyl-3-propylindole (1.0 g) in N,N-dimethylformamide (DMF) (10 ml) was added slowly to a stirred suspension of sodium hydride (0.128 g, oil-free) in dry DMF (30 ml) at 0° under an atmosphere of nitrogen. The mixture was stirred at 0° for 60 min and methyl 4-bromomethyl-3-methoxybenzoate (1.38 g) in dry DMF (10 ml) was added dropwise. The cooling bath was removed, the mixture stirred for 3.5 hr, then poured into 1N hydrochloric acid (75 ml), and extracted with ethyl acetate (15 ml). The organic extract was washed (water (twice), brine), dried (MgSO4) and evaporated to give a dark oil. The product was purified by flash chromatography, eluting with 55:40:5 hexane:methylene chloride:ethyl acetate, to give methyl 3-methoxy-4-(6-formyl-3-propylindol-1-ylmethyl)benzoate (1.9 g, 97%) as a yellow oil; partial NMR(250 MHz, DMSO-d6): 0.95(t, 3H, CH2CH3), 1.65(m, 2H, CH2CH3), 2.70(t, 2H, CH2CH2CH3), 3.83(s, 3H, OCH3), 3.95(s, 3H, OCH3), 5.50(s, 2H, NCH2), 9.96(s, 1H, CHO).

Workup

  1. customThe cooling bath was removed
  2. stirringthe mixture stirred for 3.5 hr
  3. additionpoured into 1N hydrochloric acid (75 ml)
  4. extractionextracted with ethyl acetate (15 ml)
  5. extractionThe organic extract
  6. washwas washed (water (twice), brine),
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customto give a dark oil
  10. customThe product was purified by flash chromatography
  11. washeluting with 55:40:5 hexane

Sources & evidence

ORD record
ord-bb8d5c2e585a40b5af3484c6d256826e
Source dataset
uspto-grants-1990_01
Patent number
US04894386

Reaction notes

Loading…