Ethyl Acetate → Methyl 4-(5-formylindol-3-ylmethyl)-3-methoxybenzoate

HRID 330172Notes

Reaction equation

HRID 330172 reaction equation
O.[PH2]([O-])=O.[Na+].[C:6]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2[CH2:17][C:18]1[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][C:19]=1[O:28][CH3:29])#N.[H][H].C(OCC)(=[O:34])C>O.C(O)(=O)C.N1C=CC=CC=1.[Ni]>[CH:6]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2[CH2:17][C:18]1[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][C:19]=1[O:28][CH3:29])=[O:34]

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 14882553Methyl 4-(5-cyanoindol-3-ylmethyl)-3-methoxybenzoateHCID 178418361HCID 178418361, compoundHCID 178418950HCID 178418950, compound

Product 1

HCID 14882554Methyl 4-(5-formylindol-3-ylmethyl)-3-methoxybenzoateYield 86%

Reagents, catalysts & solvents 4

HCID 935NickelCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

A solution of sodium hypophosphite monohydrate (24.8 g) in water (40 ml) was added to a solution of methyl 4-(5-cyanoindol-3-ylmethyl)-3-methoxybenzoate (11.33 g) in acetic acid (40 ml) and pyridine (80 ml). Raney nickel (approximately 2.5 g) was added as an aqueous slurry, and the mixture was heated at 50°-55° for 3 hr (CAUTION: evolution of hydrogen!). Ethyl acetate (200 ml) was added to the cooled solution, the mixture was filtered through diatomaceous earth, the filter pad washed with ethyl acetate, the combined filtrate washed with 1M hydrochloric acid (4×200 ml, until the aqueous washings were acidic), water (2×100 ml) and brine, and dried (MgSO4). The solvent was evaporated to give an oil which was purified by flash chromatography, eluting with 3:6:1 hexane:methylene chloride:ethyl acetate, giving a foam which was crystallized from a mixture of ethyl acetate and hexane to give methyl 4-(5-formylindol-3-ylmethyl)-3-methoxybenzoate (9.85 g, 86%) as white crystals; mp 117°-120°; partial NMR (250 MHz, DMSO-d6): 3.83(s, 3H, OCH3); 3.94(s, 2H, ArCH2Ar'), 8.10(s, 1H, H4 -indole), 9.94(s, 1H, CHO), 11.45 (br s, 1H, H1 -indole).

Workup

  1. filtrationthe mixture was filtered through diatomaceous earth
  2. washthe filter pad washed with ethyl acetate
  3. washthe combined filtrate washed with 1M hydrochloric acid (4×200 ml
  4. dry with materialdried (MgSO4)
  5. customThe solvent was evaporated
  6. customto give an oil which
  7. customwas purified by flash chromatography
  8. washeluting with 3:6:1 hexane
  9. custommethylene chloride:ethyl acetate, giving a foam which
  10. customwas crystallized from a mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-c7d73edd9254489a9b7778136c71b86f
Source dataset
uspto-grants-1990_01
Patent number
US04894386

Reaction notes

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