Ethyl Acetate → 4-(6-Benzyloxy-7-methoxy-3-nitroquinoline-4-carbonyl)benzonitrile

HRID 2404229Notes

Reaction equation

HRID 2404229 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[N:15]=[CH:14][C:13]([N+:21]([O-:23])=[O:22])=[C:12]2[CH:24](C#N)[C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Mn]([O-])(=O)(=O)=[O:36].[K+].C(OCC)(=O)C>O.O1CCCC1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[N:15]=[CH:14][C:13]([N+:21]([O-:23])=[O:22])=[C:12]2[C:24]([C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=1)=[O:36])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 516875Potassium PermanganateHCID 666325764-[(6-Benzyloxy-7-methoxy-3-nitroquinolin-4-yl)cyanomethyl]benzonitrile

Product 1

HCID 666328844-(6-Benzyloxy-7-methoxy-3-nitroquinoline-4-carbonyl)benzonitrileYield 74.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

4-[(6-Benzyloxy-7-methoxy-3-nitroquinolin-4-yl)cyanomethyl]benzonitrile (5.0 g, 11.1 mmol) is suspended in water (250 ml) and heated to the boil. Potassium permanganate (5.26 g, 33.3 mmol) is subsequently added in portions at such a rate that the subsequent addition is only made when the previous one has decoloured (time needed: about 2.5 h). The mixture is then heated under reflux for a further 2 h. After cooling to about 60° C., the mixture is filtered with suction. The aqueous filtrate is discarded, the filter cake is suspended four times in N,N-dimethylformamide (250 ml each time) and filtered off with suction (TLC (HPTLC) product monitoring). The combined DMF solutions are acidified to about pH 4 using 1.0 M hydrochloric acid (colour change) and evaporated to dryness in vacuo, giving an oil. The residue is taken up in tetrahydrofuran (5.0 ml), and ethyl acetate (100 ml) is subsequently added, the mixture is stirred for 30 min, and subsequently cooled in an ice bath. The precipitate obtained is filtered off with suction and dried in a high vacuum, giving 4-(6-benzyloxy-7-methoxy-3-nitroquinoline-4-carbonyl)benzonitrile (3.61 g, 8.22 mmol) as a solid having a melting point of 262° C. MS: 440.1 (M+H+), TLC (HPTLC) (HPTLC): Rf=0.44 (cyclohexane/ethyl acetate 1:1 parts by volume).

Workup

  1. temperatureheated to the boil
  2. additionthat the subsequent addition
  3. custom(time needed: about 2.5 h)
  4. temperatureThe mixture is then heated
  5. temperatureunder reflux for a further 2 h
  6. filtrationthe mixture is filtered with suction
  7. filtrationfiltered off with suction (TLC (HPTLC) product monitoring)
  8. customevaporated to dryness in vacuo
  9. customgiving an oil
  10. temperaturesubsequently cooled in an ice bath
  11. customThe precipitate obtained
  12. filtrationis filtered off with suction
  13. customdried in a high vacuum

Sources & evidence

ORD record
ord-3b63c3f0270c483b968a9539c1a0d71a
Source dataset
uspto-grants-2014_08
Patent number
US08802712B2

Reaction notes

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