Nitric Acid → HCID 20680748, compound

HRID 651621Notes

Reaction equation

HRID 651621 reaction equation
[C:1]([NH:4][C:5]1[CH:24]=[CH:23][C:8]([CH2:9][N:10]2[CH2:14][CH2:13][C@H:12]([NH:15][C:16](=[O:21])[C:17]([F:20])([F:19])[F:18])[C:11]2=[O:22])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].C(OC(=O)C)(=O)C.[N:32]([O-:34])=[O:33].[Na+].[N+]([O-])(O)=O>CC(O)=O.O>[C:1]([NH:4][C:5]1[CH:6]=[CH:7][C:8]([CH2:9][N:10]2[CH2:14][CH2:13][C@H:12]([NH:15][C:16](=[O:21])[C:17]([F:18])([F:19])[F:20])[C:11]2=[O:22])=[CH:23][C:24]=1[N+:32]([O-:34])=[O:33])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 944Nitric AcidHCID 7918Acetic AnhydrideHCID 20680749HCID 20680749, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 20680748HCID 20680748, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2,2,2-trifluoro-N-[1-(4-nitrobenzyl)-2-oxopyrrolidin-3-(S)-yl]-acetamide (0.75 g, 2.27 mmol) in AcOH (12 mL) is added acetic anhydride (1 mL) and a catalytic amount of 10% palladium on activated carbon. The heterogenous mixture is hydrogenated at room temperature on a Parr apparatus under 70 p.s.i. of H2. After 4.5 h, the reaction mixture is filtered through a pad of Celite, washed with CH2Cl2 and then MeOH. The crude product is concentrated in vacuo to yield 1.2 g of crude N-[1-(4-acetylamino-benzyl)-2-oxopyrrolidin-3-(S)-yl]-2,2,2-trifluoroacetamide as a residue (wet with HOAc). A solution of the crude N-[1-(4-acetylamino-benzyl)-2-oxopyrrolidin-3-(S)-yl]-2,2,2-trifluoroacetamide (1.2 g, wet with AcOH) in AcOH (12 mL) is cooled at 0° C. and acetic anhydride (1 mL) is added. The resulting mixture is treated with a catalytic amount of NaNO2, followed by the dropwise addition of fuming HNO3(3.8 mL). The reaction mixture is stirred at 0° C. for 1.5 hours, then at room temperature for 1.5 hours. Upon re-cooling to 0° C., a mixture of ice/ice water is added slowly with stirring. The mixture is diluted further with water and extracted with EtOAc (3×50 mL). The combined organic layers are washed twice with water. The organic phase is dried over anhydrous MgSO4, filtered and concentrated. The crude product is purified by column chromatography eluting with a gradient of 25% EtOAc/CH2Cl2 to 50% EtOAc/CH2Cl2 to provide the title compound (0.65 g, 1.67 mmol) as a beige solid.

Workup

  1. waitat room temperature for 1.5 hours
  2. temperatureUpon re-cooling to 0° C.
  3. additionis added slowly
  4. stirringwith stirring
  5. extractionextracted with EtOAc (3×50 mL)
  6. washThe combined organic layers are washed twice with water
  7. dry with materialThe organic phase is dried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product is purified by column chromatography
  11. washeluting with a gradient of 25% EtOAc/CH2Cl2 to 50% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-4cd7139df03b461ba31e8296151435de
Source dataset
uspto-grants-2001_08
Patent number
US06281227B1

Reaction notes

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