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

HRID 231602Notes

Reaction equation

HRID 231602 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 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 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-7dc98b7bb6c24f21b2f433180364a3c7
Source dataset
uspto-grants-1989_07
Patent number
US04847273

Reaction notes

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