Acetone → N-(1-ethyl-2-pyrrolidinylmethyl)-2-methyl-5-sulfamoyl-2,3-dihydrobenzofuran-7-carboxamide

HRID 2290582Notes

Reaction equation

HRID 2290582 reaction equation
[CH3:1][CH:2]1[CH2:6][C:5]2[CH:7]=[C:8]([S:14](=[O:17])(=[O:16])[NH2:15])[CH:9]=[C:10]([C:11]([OH:13])=O)[C:4]=2[O:3]1.[CH3:18][N:19](C)C=O.CC(C)=O.C(Cl)(=O)OCC.[CH2:33]([N:35]([CH2:38][CH3:39])[CH2:36][CH3:37])[CH3:34]>O>[CH2:33]([N:35]1[CH2:38][CH2:39][CH2:37][CH:36]1[CH2:18][NH:19][C:11]([C:10]1[C:4]2[O:3][CH:2]([CH3:1])[CH2:6][C:5]=2[CH:7]=[C:8]([S:14](=[O:17])(=[O:16])[NH2:15])[CH:9]=1)=[O:13])[CH3:34]

Participants

7

Reactant 5

HCID 180AcetoneHCID 6228DimethylformamideHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 136908862-Methyl-5-sulfamoyl-2,3-dihydrobenzofuran-7-carboxylic acid

Product 1

HCID 13420575N-(1-ethyl-2-pyrrolidinylmethyl)-2-methyl-5-sulfamoyl-2,3-dihydrobenzofuran-7-carboxamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
15 °C

Procedure

To a solution of 6 g of (-)-2-methyl-5-sulfamoyl-2,3-dihydrobenzofuran-7-carboxylic acid [[α]D =-17.04° (dimethylformamide, c=1)] in a mixed solvent of 55 ml of dimethylformamide and 55 ml of acetone is added 5.9 g of triethylamine and the whole is stirred. The solution is cooled to 15° C., and 2.7 g of ethyl chlorocarbonate is added dropwise for 10 minutes. After stirring at room temperature for 40-45 minutes, 7.5 g of (-)-2-aminomethyl-1-ethylpryrrolidine is added and the reactant is stirred at room temperature for 20 minutes and allowed to stand overnight. Excess triethylamine and acetone are distilled off under diminished pressure and the residue obtained is poured with stirring into 500-600 ml of water. Precipitated crystals are collected by suction filtration, washed with water and dried. The filtrate, aqueous layer is extracted with ethyl acetate three times and the extract layer is washed with water and dried. Ethyl acetate is distilled off under reduced pressure to afford crude crystals. Both the crude crystals are combined and recrystallized from ethyl acetate to give crystals of N-(1-ethyl-2-pyrrolidinylmethyl)-2-methyl-5-sulfamoyl-2,3-dihydrobenzofuran-7-carboxamide, m.p. 155°-156° C., [α]D =-64.671° (dimethylformamide, c=1), which is an optically active compound.

Workup

  1. stirringAfter stirring at room temperature for 40-45 minutes
  2. addition7.5 g of (-)-2-aminomethyl-1-ethylpryrrolidine is added
  3. stirringthe reactant is stirred at room temperature for 20 minutes
  4. distillationExcess triethylamine and acetone are distilled off under diminished pressure
  5. customthe residue obtained
  6. additionis poured
  7. customPrecipitated crystals
  8. filtrationare collected by suction filtration
  9. washwashed with water
  10. customdried
  11. extractionThe filtrate, aqueous layer is extracted with ethyl acetate three times
  12. washthe extract layer is washed with water
  13. customdried
  14. distillationEthyl acetate is distilled off under reduced pressure
  15. customto afford crude crystals
  16. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-5d41397b26934729a660931254394c17
Source dataset
uspto-grants-1986_10
Patent number
US04617314

Reaction notes

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