Sodium Chloride → (E)-5-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-3-oxopent-4-enoic acid methyl ester

HRID 352093Notes

Reaction equation

HRID 352093 reaction equation
[CH3:1][O:2][C:3](=[O:29])[CH:4]=[C:5](C)[CH2:6][CH:7]([C:9]1[N:10]([CH:25]([CH3:27])[CH3:26])[C:11]2[C:16]([C:17]=1[C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1)=[CH:15][CH:14]=[CH:13][CH:12]=2)C.C(N(CC)CC)C.[OH-:37].[NH4+].[Cl-].[Na+]>C1COCC1>[CH3:1][O:2][C:3](=[O:29])[CH2:4][C:5](=[O:37])/[CH:6]=[CH:7]/[C:9]1[N:10]([CH:25]([CH3:26])[CH3:27])[C:11]2[C:16]([C:17]=1[C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1)=[CH:15][CH:14]=[CH:13][CH:12]=2

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 8471TriethylamineHCID 14923Ammonium HydroxideHCID 698920535-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-3-methylhex-2-enoic acid methyl ester

Product 1

HCID 11326444(E)-5-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-3-oxopent-4-enoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a 2 liter round-bottomed flask equipped with a magnetic stirrer and nitrogen delivery line, 30.5 g of crude 5-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-3-methylhex-2-enoic acid methyl ester are dissolved in 250 ml of THF, 13.49 g (133.3 mmol) of triethylamine are added and the yellow solution is heated under reflux for 2 hours. The reaction mixture is then cooled to room temperature, 53 ml (212 mmol) of 4N ammonium hydroxide solution are added and the mixture is stirred vigorously for 3 hours. The reaction mixture is then poured into 1 liter of saturated sodium chloride solution and extracted three times with 250 ml of ethyl acetate. The combined organic phases are washed once with 100 ml of 1N hydrochloric acid and three times with saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated by evaporation. The crude product (22.78 g of an orange resin) is purified by means of flash chromatography (hexane/ethyl acetate=9:1). A resin is obtained which, according to NMR, is the product in a keto-enol equilibrium of approximately 3:1.

Workup

  1. customIn a 2 liter round-bottomed flask equipped with a magnetic stirrer
  2. temperaturethe yellow solution is heated
  3. temperatureunder reflux for 2 hours
  4. extractionextracted three times with 250 ml of ethyl acetate
  5. washThe combined organic phases are washed once with 100 ml of 1N hydrochloric acid and three times with saturated sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated by evaporation
  9. customThe crude product (22.78 g of an orange resin) is purified by means of flash chromatography (hexane/ethyl acetate=9:1)
  10. customA resin is obtained which

Sources & evidence

ORD record
ord-fb82e8271ddc405ea062a1a65c7d47ff
Source dataset
uspto-grants-2004_06
Patent number
US06743926B2

Reaction notes

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