Hydrochloric Acid → Methyl 4-[5-(3-carboxy-2,3,4,5-tetrahydro-5-oxofuran-2-yl)-1-propylindol-3-ylmethyl]-3-methoxybenzoate

HRID 330202Notes

Reaction equation

HRID 330202 reaction equation
C(N(CC)CC)C.[CH:8]([C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[N:15]([CH2:19][CH2:20][CH3:21])[CH:14]=[C:13]2[CH2:22][C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][C:24]=1[O:33][CH3:34])=[O:9].[C:35]1(=[O:41])[O:40][C:38](=[O:39])[CH2:37][CH2:36]1.Cl>C(Cl)Cl.[Cl-].[Zn+2].[Cl-].C(OCC)(=O)C>[C:38]([CH:37]1[CH2:36][C:35](=[O:41])[O:9][CH:8]1[C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[N:15]([CH2:19][CH2:20][CH3:21])[CH:14]=[C:13]2[CH2:22][C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][C:24]=1[O:33][CH3:34])([OH:40])=[O:39]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7922Succinic anhydrideHCID 8471TriethylamineHCID 14882683Methyl 4-(5-formyl-1-propylindol-3-ylmethyl)-3-methoxybenzoate

Product 1

HCID 19870632Methyl 4-[5-(3-carboxy-2,3,4,5-tetrahydro-5-oxofuran-2-yl)-1-propylindol-3-ylmethyl]-3-methoxybenzoate

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Triethylamine (8.32 g) was added slowly to a stirred mixture of methyl 4-[5-formyl-1-propylindol-3-ylmethyl]-3-methoxybenzoate (10 g), succinic anhydride (5.5 g) and zinc chloride (11.4 g) in methylene chloride (50 ml), under a nitrogen atmosphere, such that the temperature of the reaction did not exceed 25°. After complete addition, the mixture was stirred for 15 hr, poured into a mixture of 2M hydrochloric acid (500 ml) and ethyl acetate (500 ml), the layers separated and the aqueous layer extracted with ethyl acetate. The combined extracts were washed (water (three times), brine), dried (MgSO4) and evaporated. The product was dissolved in aqueous sodium bicarbonate (300 ml, 6% w/v), and the solution extracted with ether. The aqueous layer was neutralized with 6M hydrochloric acid, acidified to pH 4 with 1M hydrochloric acid, and extracted with ethyl acetate. The extracts were washed (water (twice), brine), dried (MgSO4) and evaporated to give methyl 4-[5-(3-carboxy-2,3,4,5-tetrahydro-5-oxofuran-2-yl)-1-propylindol-3-ylmethyl]-3-methoxybenzoate (12.36 g, 97%, as a mixture of diastereomers) as an off-white foam: partial NMR (300 MHz, DMSO-d6): 0.83(m, 3H, CH3, both isomers), 3.83(s, 3H, OCH3, both isomers), 3.91(s, 3H, OCH3, both isomers), 5.61(d, 0.5H, CHOC(O), isomer A), 5.87(d, 0.5H, CHOC(O) isomer B).

Workup

  1. customdid not exceed 25°
  2. additionAfter complete addition
  3. customthe layers separated
  4. extractionthe aqueous layer extracted with ethyl acetate
  5. washThe combined extracts were washed (water (three times), brine)
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. dissolutionThe product was dissolved in aqueous sodium bicarbonate (300 ml, 6% w/v)
  9. extractionthe solution extracted with ether
  10. extractionextracted with ethyl acetate
  11. washThe extracts were washed (water (twice), brine),
  12. dry with materialdried (MgSO4)
  13. customevaporated

Sources & evidence

ORD record
ord-977d7c7b5ba04e2caed08ca7c5deb11a
Source dataset
uspto-grants-1990_01
Patent number
US04894386

Reaction notes

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