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

HRID 73654Notes

Reaction equation

HRID 73654 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][C:16]([N+:19]([O-:21])=[O:20])=[C:15]([F:22])[CH:14]=1)#[N:2].[H-].[Na+].[NH2:25]OP(=O)(C1C=CC=CC=1)C1C=CC=CC=1>CN(C=O)C>[NH2:25][N:7]1[C:3]([C:1]#[N:2])=[C:4]([C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[C:15]([F:22])[CH:14]=2)[C:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10955453O-(Diphenylphosphinyl)hydroxylamine2×HCID 57758340ethyl 5-cyano-4-(3-fluoro-4-nitrophenyl)-1H-pyrrole-3-carboxylate

Product 1

HCID 57757940ethyl 1-amino-5-cyano-4-(3-fluoro-4-nitrophenyl)-1H-pyrrole-3-carboxylateYield 71.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of ethyl 5-cyano-4-(3-fluoro-4-nitrophenyl)-1H pyrrole-3-carboxylate (31.9 g, 105.2 mmol) in DMF (1.5 L) was slowly added NaH (34.54 g, 136.7 mmol). After the evolution of gas had ceased (aminooxy)(diphenyl)phosphine oxide (34.4 g, 147.3 mmol) was added in one portion. Upon addition of (aminooxy)(diphenyl)phosphine oxide the reaction mixture solidified. The reaction mixture was heated to 80° C. during which time the solids broke up and mixture stirred freely. The reaction was heated for 3 h, then cooled and the DMF was removed under reduced pressure. The remaining slurry was dissolved in EtOAc (500 mL) and filtered to remove a majority of the phosphinic acid. The filter cake was washed with EtOAc and the organics were concentrated in vacuo. The product was purified by crystallization from hot ACN to provide a tan solid (24.0 g, 75.31 mmol) in 71% yield. 1H-NMR (DMSO-d6) δ 8.21 (app t, J=8.4 Hz, 1H), 7.73 (s, 1H), 7.71 (dd, J=12.4, 2.0 Hz, 1H), 7.48 (m, 1H), 6.72 (s, 2H), 4.11 (q, J=7.2 Hz, 2H), 1.14 (t, J=7.2 Hz, 3H).

Workup

  1. additionwas added in one portion
  2. temperatureThe reaction was heated for 3 h
  3. temperaturecooled
  4. customthe DMF was removed under reduced pressure
  5. dissolutionThe remaining slurry was dissolved in EtOAc (500 mL)
  6. filtrationfiltered
  7. customto remove a majority of the phosphinic acid
  8. washThe filter cake was washed with EtOAc
  9. concentrationthe organics were concentrated in vacuo
  10. customThe product was purified by crystallization from hot ACN

Sources & evidence

ORD record
ord-1fdf5aa200af4727b34d964170411c1c
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Reaction notes

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