Dimethyl Sulfate → Ethyl 1-methyl-4-nitro-3-methoxypyrrole-2-carboxylate

HRID 988001Notes

Reaction equation

HRID 988001 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([N+:7]([O-:9])=[O:8])[C:4]([OH:10])=[C:3]1[C:11]([O:13][CH2:14][CH3:15])=[O:12].S(OC)(O[CH3:20])(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.C(Cl)Cl>[CH3:1][N:2]1[CH:6]=[C:5]([N+:7]([O-:9])=[O:8])[C:4]([O:10][CH3:20])=[C:3]1[C:11]([O:13][CH2:14][CH3:15])=[O:12]

Participants

6

Reactant 3

HCID 6497Dimethyl SulfateHCID 11430Potassium CarbonateHCID 54696575ethyl 3-hydroxy-1-methyl-4-nitro-1H-pyrrole-2-carboxylate

Product 1

HCID 9877941Ethyl 1-methyl-4-nitro-3-methoxypyrrole-2-carboxylateYield 89%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of ethyl 1-methyl-4-nitro-3-hydroxypyrrole-2-carboxylate (0.071 g, 0.3315 mmol), dimethyl sulfate (0.055 g, 0.436 mmol) and anhydrous potassium carbonate (0.5 g, 3.90 mmol) in dry acetone (20 mL) was refluxed under a nitrogen atmosphere for 22 h. Potassium carbonate was removed by filtration and the filtrate was evaporated under reduced pressure to afford an orange crystalline solid. Excess dimethyl sulfate was destroyed by treating the residue with aqueous ammonia (1 mL). Water (2 mL) was added and the residue was extracted with ether (30 mL). The combined ether extracts were washed with aqueous sodium hydroxide solution and water. Removal of ether under reduced pressure afforded a cream residue. The residue was dissolved in CH2Cl2 (25 mL), dried with anhydrous Na2SO41 filtered and evaporated under reduced pressure to yield a cream microcrystalline solid (0.067 g, 89%). Recrystallization from acetone/hexane afforded colorless needles, mp 145-147° C.; 1H NMR (300 MHZ, CDCl3) d 1.40 (t, J=7.2 Hz, 3H, CH3—CH2—), 3.90 (s, 3H, CH3—N—), 3.95 (s, 3H, CH3O—), 4.36 (q, J=7.0 Hz, 2H, CH3—CH2—), 7.47 (s, 1H, H-5); 13C NMR (100 MHZ, CDCl3) d 14.22, 38.92, 60.67, 63.02, 114.73, 125.76, 127.79, 146.18, 160.09; MS (EI, 70 eV) m/z (relative intensity) 229 (M+1, 3), 228 (M+, 30), 211 (12), 183 (12), 167 (20), 153 (25), 152 (100), 141 (7), 109 (12), 84 (8), 67 (6), 53 (31), 42 (17), Calcd for C9H12N2O5: 228.20. HRMS (M+H): Calcd for C9H13N2O5 [M+H+]: 229.0824, Found 229.0834. Anal. Calcd for C9H12N2O5: C, 47.37; H, 5.29; N, 12.27. Found. C, 47.44; H, 5.36; N, 12.28. TLC (ethyl acetate/Hexane, 1:3) Rf 0.23.

Workup

  1. temperaturewas refluxed under a nitrogen atmosphere for 22 h
  2. customPotassium carbonate was removed by filtration
  3. customthe filtrate was evaporated under reduced pressure
  4. customto afford an orange crystalline solid
  5. customExcess dimethyl sulfate was destroyed
  6. additionby treating the residue with aqueous ammonia (1 mL)
  7. additionWater (2 mL) was added
  8. extractionthe residue was extracted with ether (30 mL)
  9. washThe combined ether extracts were washed with aqueous sodium hydroxide solution and water
  10. customRemoval of ether under reduced pressure
  11. customafforded a cream residue
  12. customdried with anhydrous Na2SO41
  13. filtrationfiltered
  14. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-015b43e480b645229bf7d53ce658d44c
Source dataset
uspto-grants-2003_10
Patent number
US06632950B2

Reaction notes

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