Sodium hydride → ethyl 1-amino-1H-imidazole-2-carboxylate

HRID 1487294Notes

Reaction equation

HRID 1487294 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]([O:8][CH2:9][CH3:10])=[O:7].[H-].[Na+].[NH2:13]OP(=O)(C1C=CC=CC=1)C1C=CC=CC=1.C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1>CN(C=O)C>[NH2:13][N:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]([O:8][CH2:9][CH3:10])=[O:7]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 73910Diphenylphosphinic chlorideHCID 549404ethyl 1H-imidazole-2-carboxylateHCID 10955453O-(Diphenylphosphinyl)hydroxylamine

Product 1

HCID 58332105ethyl 1-amino-1H-imidazole-2-carboxylateYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of ethyl 1H-imidazole-2-carboxylate (2.00 g, 14.27 mmol) in DMF (40 mL) at 0° C. was added sodium hydride (0.714 g, 17.84 mmol, 60% wt). The reaction solution was stirred at room temperature for 120 min and then was cooled to 0° C. A suspension of (aminooxy)diphenylphosphine oxide [4.66 g, 19.98 mmol, prepared from diphenylphosphinic chloride following a known procedure (Org. Lett., 351-353 (2007))], in DMF (70 ml) was added. After 10 min, the ice bath was removed. The reaction mixture became viscous and stirred at room temperature for 3 h. The reaction was quenched with water until it became a clear solution, and concentrated to dryness under reduced pressure. The crude product was suspended in EtOAc (400 ml) with stirring for 30 min and filtered. The filtrate was concentrated to give a pale yellow viscous solid, 2.6 g. The crude product was purified via silica gel column (Isco prep: 0-5% MeOH-DCM over 20 minutes) to afford ethyl 1-amino-1H-imidazole-2-carboxylate (1.99 g, 90% yield) as a white solid. 1H NMR (400 MHz, MeOD) δ 7.35 (d, J=1.3 Hz, 1H), 7.11 (s, 1H), 4.37 (q, J=7.3 Hz, 2H), 1.50 (br. s., 9H), 1.38 (t, J=7.0 Hz, 4H). ESI-MS (analytical LCMS Method A): m/z 156.0 ([M+H]+).

Workup

  1. temperaturewas cooled to 0° C
  2. additionwas added
  3. waitAfter 10 min
  4. customthe ice bath was removed
  5. stirringstirred at room temperature for 3 h
  6. customThe reaction was quenched with water until it
  7. concentrationconcentrated to dryness under reduced pressure
  8. stirringwith stirring for 30 min
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated
  11. customto give a pale yellow viscous solid, 2.6 g
  12. customThe crude product was purified via silica gel column (Isco prep: 0-5% MeOH-DCM over 20 minutes)

Sources & evidence

ORD record
ord-5b2ef76086724a4487027a78d28ce635
Source dataset
uspto-grants-2016_08
Patent number
US09428511B2

Reaction notes

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