Tetrahydrofuran → ethyl 1-amino-1H-imidazole-2-carboxylate

HRID 1487295Notes

Reaction equation

HRID 1487295 reaction equation
[Li]N([Si](C)(C)C)[Si](C)(C)C.C1COCC1.[NH:16]1[CH:20]=[CH:19][N:18]=[C:17]1[C:21]([O:23][CH2:24][CH3:25])=[O:22].[NH2:26]OP(=O)(C1C=CC=CC=1)C1C=CC=CC=1>CN(C=O)C>[NH2:26][N:16]1[CH:20]=[CH:19][N:18]=[C:17]1[C:21]([O:23][CH2:24][CH3:25])=[O:22]

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 549404ethyl 1H-imidazole-2-carboxylateHCID 2733832Lithium HexamethyldisilazideHCID 10955453O-(Diphenylphosphinyl)hydroxylamineHCID 178418261HCID 178418261, compound

Product 1

HCID 58332105ethyl 1-amino-1H-imidazole-2-carboxylateYield 93%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Alternative procedure using 1M LiN(TMS)2 as base: A 1M THF solution of LiHMDS (19.62 ml, 19.62 mmol) was added dropwise to a solution of ethyl 1H-imidazole-2-carboxylate (2.5 g, 17.84 mmol) in DMF (119 ml) at 0° C. The reaction was stirred at 0° C. for 10 minutes. A DMF (119 ml) suspension of (aminooxy)diphenylphosphine oxide (4.99 g, 21.41 mmol) was added. After stirring for 10 minutes, the ice bath was removed, and stirring was continued at room temperature. After 3 hrs, the starting material was completely consumed. Water was added portion-wise to the reaction mixture until complete dissolution of the suspension. The clear solution was concentrated to dryness under reduced pressure. Ethyl acetate was added to the solid, forming a yellow suspension. The suspension was stirred for 15 minutes and filtered. The solid was washed with ethyl acetate and dichloromethane, successively. The collected organic wash was concentrated. The crude product was dissolved in 10% MeOH/DCM (10 ml) and was chromatographed on a prepacked silica gel column (Isco prep: 0-5% MeOH-DCM over 20 minutes. The product began eluting around 7 minutes (˜2% MeOH/DCM). The desired ethyl 1-amino-1H-imidazole-2-carboxylate (2.57 g, 16.56 mmol, 93% yield) was obtained as a white solid.

Workup

  1. additionwas added
  2. stirringAfter stirring for 10 minutes
  3. customthe ice bath was removed
  4. stirringstirring
  5. customwas continued at room temperature
  6. waitAfter 3 hrs
  7. customthe starting material was completely consumed
  8. additionWater was added portion-wise to the reaction mixture
  9. dissolutionuntil complete dissolution of the suspension
  10. concentrationThe clear solution was concentrated to dryness under reduced pressure
  11. additionEthyl acetate was added to the solid
  12. customforming a yellow suspension
  13. stirringThe suspension was stirred for 15 minutes
  14. filtrationfiltered
  15. washThe solid was washed with ethyl acetate and dichloromethane
  16. washThe collected organic wash
  17. concentrationwas concentrated
  18. dissolutionThe crude product was dissolved in 10% MeOH/DCM (10 ml)
  19. customwas chromatographed on a prepacked silica gel column (Isco prep
  20. wait0-5% MeOH-DCM over 20 minutes
  21. washThe product began eluting around 7 minutes (˜2% MeOH/DCM)

Sources & evidence

ORD record
ord-08fe0326890246349bded6f7b4fe38d6
Source dataset
uspto-grants-2016_08
Patent number
US09428511B2

Reaction notes

Loading…