Acetic Acid → Ethyl 3-amino-1H-pyrrole-2-carboxylate

HRID 751248Notes

Reaction equation

HRID 751248 reaction equation
O1C=CC=[N:2]1.[C:6](O)(=O)[CH3:7].Cl.[NH2:11][CH:12]([C:18](OCC)=O)[C:13]([O:15][CH2:16][CH3:17])=[O:14].C([O-])(=O)C.[Na+]>C(O)C.[O-]CC.[Na+]>[NH2:2][C:18]1[CH:7]=[CH:6][NH:11][C:12]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14]

Participants

7

Reactant 4

HCID 176Acetic Acid2×HCID 9254IsoxazoleHCID 517045Sodium AcetateHCID 3084143Propanedioic acid, 2-amino-, 1,3-diethyl ester, hydrochloride (1:1)

Product 1

HCID 2773439Ethyl 3-amino-1H-pyrrole-2-carboxylateYield 106%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent4×HCID 2723922Sodium ethoxideSolvent2×

Procedure

A solution of sodium ethoxide in ethanol (2M, 152 mL, 305 mmol) was added slowly to a stirred solution of isoxazole 18 (20 g, 290 mmol) in ethanol (80 mL) in an ice bath with the reaction temperature ≦8° C. After an additional 0.5 h with stirring, acetic acid (5.5 mL, 100 mmol), diethyl aminomalonate hydrochloride (40.9 g, 193 mmol) and sodium acetate (16.4 g, 200 mmol) were added and the mixture was stirred at room temperature for 2 days after which most of the ethanol was removed under vacuum. The residue was partitioned between chloroform and water and the organic phase was dried and filtered through a pad of silica gel. Evaporation afforded a syrup which was dissolved in a solution of sodium ethoxide in ethanol (0.5 M, 400 mL) and the solution was stirred at room temperature for 3 days. Acetic acid (12 mL, 210 mmol) was added and the ethanol removed under vacuum. The residue was dissolved in chloroform and washed with NaHCO3 (aq., pH kept ˜7) The organic phase was dried and filtered through a thick pad of silica gel to give crude syrupy 3-amino-2-ethoxycarbonylpyrrole (16.4 g, 106 mmol) with clean 1H and 13C NMR spectra that was suitable for synthetic use. A portion in ether was treated with HCl in dioxane to precipitate the corresponding hydrochloride salt. Recrystallized from ethyl acetate/ethanol it had mp 197-200° C.; 1H NMR (d6-DMSO), δ 7.02 (t, J=3.0 Hz, 1H), 6.34 (t, J=2.5 Hz, 1H), 4.26 (q, J=7.1 Hz, 2H), 1.31 (t, J=7 Hz, 3H). 13C NMR δ 159.7, 123.2, 121.6, 114.7, 106.1, 60.6, 14.6. Anal. Calcd for C7H11ClN2O5: C, 44.10; H, 5.82; N, 14.70. Found: C, 44.02; H, 6.13; N, 14.55.

Workup

  1. customwas removed under vacuum
  2. customThe residue was partitioned between chloroform and water
  3. customthe organic phase was dried
  4. filtrationfiltered through a pad of silica gel
  5. customEvaporation
  6. customafforded a syrup which
  7. stirringthe solution was stirred at room temperature for 3 days
  8. customthe ethanol removed under vacuum
  9. dissolutionThe residue was dissolved in chloroform
  10. washwashed with NaHCO3 (aq., pH kept ˜7) The organic phase
  11. customwas dried
  12. filtrationfiltered through a thick pad of silica gel

Sources & evidence

ORD record
ord-704f3008211e4070908eb5e719531d46
Source dataset
uspto-grants-2008_07
Patent number
US07405297B2

Reaction notes

Loading…