Isopropanol → 1,4-Dihydro-2,6-dimethyl-5-[(2-methoxyethyl)methylsulfamoyl]-4-(3-nitrophenyl)nicotinic acid 2-propoxyethyl ester

HRID 982292Notes

Reaction equation

HRID 982292 reaction equation
C([C:4]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N+:21]([O-:23])=[O:22])[CH:16]=1)=[CH:5][S:6]([N:9]([CH2:11][CH2:12][O:13][CH3:14])[CH3:10])(=[O:8])=[O:7])(=O)C.[CH2:24]([O:27][CH2:28][CH2:29][O:30][C:31](=[O:36])/[CH:32]=[C:33](\[NH2:35])/[CH3:34])[CH2:25][CH3:26].[CH:37](O)(C)[CH3:38]>>[CH2:24]([O:27][CH2:28][CH2:29][O:30][C:31](=[O:36])[C:32]1[CH:4]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([N+:21]([O-:23])=[O:22])[CH:16]=2)[C:5]([S:6](=[O:7])(=[O:8])[N:9]([CH2:11][CH2:12][O:13][CH3:14])[CH3:10])=[C:37]([CH3:38])[NH:35][C:33]=1[CH3:34])[CH2:25][CH3:26]

Participants

4

Reactant 3

HCID 3776IsopropanolHCID 125291902-(n-Propoxy)ethyl 3-aminocrotonateHCID 53932152alpha-acetyl-N-(2-methoxyethyl)-N-methyl-3-nitrostyrenesulfonamide

Product 1

HCID 679460421,4-Dihydro-2,6-dimethyl-5-[(2-methoxyethyl)methylsulfamoyl]-4-(3-nitrophenyl)nicotinic acid 2-propoxyethyl esterYield 47%

Procedure

A solution of 3.42 g (0.01 mol) of α-acetyl-N-(2- -methoxyethyl)-N-methyl-3-nitrostyrenesulfonamide and 1.87 g (0.01 mol) of 3-aminocrotonic acid 2-propoxyethyl ester in 15 ml of isopropanol is heated to reflux for 2 hours, thereupon treated with 1.0 g of Amberlyst® 15 as the catalyst and then heated to reflux for an additional 30 minutes. After concentration under reduced pressure 0 the oily residue is dissolved in methylene chloride, the catalyst remaining behind is removed by filtration under suction, and the filtrate is washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated to dryness. The residual oil is chromatographed on 300 g of silica gel with methylene chloride/ethyl acetate (4:1) as the elution agent. The uniform fractions yield an oil which crystallizes upon trituration and leaving to stand under hexane. After recrystallization from ether, there are obtained 2.4 g (47%) of 1,4-dihydro-2 6-dimethyl-5-[(2-methoxyethyl)methylsulfamoyl]-4-(3-nitrophenyl)nicotinic acid 2-propoxyethyl ester. m.p. 67°-70°, as an almost colorless crystalline powder.

Workup

  1. temperatureto reflux for 2 hours
  2. additiontreated with 1.0 g of Amberlyst® 15 as the catalyst
  3. temperatureheated
  4. temperatureto reflux for an additional 30 minutes
  5. concentrationAfter concentration under reduced pressure 0 the oily residue
  6. dissolutionis dissolved in methylene chloride
  7. customthe catalyst remaining behind is removed by filtration under suction
  8. washthe filtrate is washed with a saturated aqueous sodium chloride solution
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated to dryness
  11. customThe residual oil is chromatographed on 300 g of silica gel with methylene chloride/ethyl acetate (4:1) as the elution agent
  12. customThe uniform fractions yield an oil which
  13. customcrystallizes upon trituration
  14. customleaving
  15. customAfter recrystallization from ether, there

Sources & evidence

ORD record
ord-d8d5f8050a7e46759e09bf0dea4e0d4b
Source dataset
uspto-grants-1991_02
Patent number
US04994612

Reaction notes

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