Sodium hydride → ethyl 1-amino-5-cyano-4-(nitrophenyl)-1H-pyrrole-3-carboxylate

HRID 73649Notes

Reaction equation

HRID 73649 reaction equation
[C:1]([C:3]1[NH:7][CH:6]=[C:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:4]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[N+:19]([O-:21])=[O:20])#[N:2].[H-].[Na+].[NH2:24]OP(=O)(C1C=CC=CC=1)C1C=CC=CC=1>CN(C=O)C>[NH2:24][N:7]1[C:3]([C:1]#[N:2])=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N+:19]([O-:21])=[O:20])[C:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10955453O-(Diphenylphosphinyl)hydroxylamineHCID 66641241ethyl 5-cyano-4-(nitrophenyl)-1H-pyrrole-3-carboxylate

Product 1

HCID 66641198ethyl 1-amino-5-cyano-4-(nitrophenyl)-1H-pyrrole-3-carboxylateYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A 3 L 3 neck round bottomed flask was fitted with a reflux condenser and overhead stirrer and charged with ethyl 5-cyano-4-(nitrophenyl)-1H-pyrrole-3-carboxylate (20 g, 70.11 mmol). To a rapidly stirred solution in DMF (1 L) was added NaH (5×500 mg, 98 mmol) portion wise over 20 min. The dark brown solution was allowed to stir for an additional 10 min. The aminating reagent ((aminooxy)(diphenyl)phosphine oxide) was added in one portion (21.26 g, 91.14 mmol). The reaction mixture immediately solidified. Upon heating to 60° C. the solids began to disperse. The mixture was eventually heated to 80° C. and stirred over night. The reaction mixture was cooled and the solids were filtered off. The filter cake was washed with EtOAc (200 mL) and the filtrate was concentrated in vacuo. The resulting solid was suspended in Et2O (300 mL) and filtered to provide a 69% yield of the product (14.37 g, 47.86 mmol) as a light tan powder. The product was used without further purification. 1H-NMR (DMSO-d6) δ 8.29-8.24 (m, 2H), 7.72 (s, 1H), 7.71-7.68 (m, 2H), 6.71 (s, 2H), 4.09 (q, J=7.2 Hz, 2H), 1.12 (t, J=7.2 Hz, 3H); HPLC RT=3.15 min.

Workup

  1. additionto disperse
  2. temperatureThe mixture was eventually heated to 80° C.
  3. stirringstirred over night
  4. temperatureThe reaction mixture was cooled
  5. filtrationthe solids were filtered off
  6. washThe filter cake was washed with EtOAc (200 mL)
  7. concentrationthe filtrate was concentrated in vacuo
  8. filtrationfiltered

Sources & evidence

ORD record
ord-7444a41d13884559b3c9bdd6a9ad3b14
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Reaction notes

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