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

HRID 2197517Notes

Reaction equation

HRID 2197517 reaction equation
[H-].[Na+].[C:3]([C:5]1[NH:9][CH:8]=[C:7]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:6]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N+:21]([O-:23])=[O:22])#[N:4].[NH2:24]OP(=O)(C1C=CC=CC=1)C1C=CC=CC=1.[Na]>CN(C=O)C.C(OCC)(=O)C>[NH2:24][N:9]1[C:5]([C:3]#[N:4])=[C:6]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[N+:21]([O-:23])=[O:22])[C:7]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:8]1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 5360545SodiumHCID 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 75%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Sodium hydride (60% dispersion in mineral oil, 3.02 g, 75.6 mmol) was added to a solution ethyl 5-cyano-4-(nitrophenyl)-1H-pyrrole-3-carboxylate (17.97 g, 63.00 mmol) in DMF (625 mL). The solution was stirred at it for 15 min and then (aminooxy)(diphenyl)phosphine oxide (17.63 g, 75.59 mmol) was added, and the solution was heated (80° C.) for 17 h. Upon cooling to it aqueous saturated sodium bircarbonate solution (500 mL) was added followed by ethyl acetate (400 mL). The layers were separated and the aqueous layer was back extracted with ethyl acetate (2×200 mL). The combined organic layers dried over sodium sulfate and concentrated to dryness. The crude material was triturated with dichloromethane-hexanes (1:1 v/v 400 mL). The solid was collected, washed with hexanes (100 mL), and dried under vacuum. The material was suspended in ethyl acetate (500 mL) and, heated to reflux for 15 min, and then filtered. The filtrate was concentrated in vacuo to afford the desired product (14.15 g, 75%). 1H-NMR (300 MHz, DMSO-d6) 8.25-8.31 (m, 2H), 7.73 (s, 1H), 7.67-7.73 (m, 2H), 6.71 (br s, 2H), 4.12 (q, J=7.1 Hz, 2H), 1.16 (t, J=7.1 Hz, 3H); HPLC RT (Method A) 2.91 min; TLC Rf=0.30 (95:5 v/v CH2Cl2-EtOAc).

Workup

  1. additionwas added
  2. customThe layers were separated
  3. extractionthe aqueous layer was back extracted with ethyl acetate (2×200 mL)
  4. dry with materialThe combined organic layers dried over sodium sulfate
  5. concentrationconcentrated to dryness
  6. customThe crude material was triturated with dichloromethane-hexanes (1:1 v/v 400 mL)
  7. customThe solid was collected
  8. washwashed with hexanes (100 mL)
  9. customdried under vacuum
  10. temperatureheated
  11. temperatureto reflux for 15 min
  12. filtrationfiltered
  13. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-51b8ef8211f643948707f77700f03f36
Source dataset
uspto-grants-2012_12
Patent number
US08338594B2

Reaction notes

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