4-Chloro-6,7-dimethoxy-3-nitroquinoline → HCID 619079, compound

HRID 2404234Notes

Reaction equation

HRID 2404234 reaction equation
[Zn](C)[CH3:2].Cl[C:5]1[C:14]2[C:9](=[CH:10][C:11]([O:17][CH3:18])=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]=[CH:7][C:6]=1[N+:19]([O-:21])=[O:20]>O.O=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:16][O:15][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][C:11]=1[O:17][CH3:18])[N:8]=[CH:7][C:6]([N+:19]([O-:21])=[O:20])=[C:5]2[CH3:2]

Participants

6

Reactant 2

HCID 226465674-Chloro-6,7-dimethoxy-3-nitroquinolineHCID 178477796HCID 178477796, compound

Product 1

HCID 619079HCID 619079, compoundYield 127.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 977OxygenSolvent

Conditions

Temperature
80 °C

Procedure

Zn(CH3)2 (1.2 M in toluene, 15.35 ml, 18.43 mmol) and Pd(dppf)Cl2 (2.28 g, 2.92 mmol) are added to a solution of 4-chloro-6,7-dimethoxy-3-nitroquinoline (7.5 g, 27.92 mmol) in water- and oxygen-free dioxane (200 ml, pre-treatment: nitrogen gas passed through for 30 min). The reaction mixture is heated at 80° C. for 8 h, giving a solution. After cooling to room temperature, water (65 ml) is slowly added, and the mixture is extracted with ethyl acetate (60 ml). After separation, the organic phase is washed with a little hydrochloric acid (1.0 M, 5 ml). The aqueous phase is extracted three times with ethyl acetate (60 ml each time). The combined organic phases are dried over Na2SO4, filtered with suction and evaporated to dryness in vacuo. The residue is purified by chromatography over flash silica gel (solvent cyclohexane/ethyl acetate 2:1, parts by volume), giving 6,7-dimethoxy-4-methyl-3-nitroquinoline (5.82 g, 23.44 mmol) as a solid. MS: 249.0 (M+H+), TLC (HPTLC): Rf=0.45 (cyclohexane/ethyl acetate 1:1, parts by volume).

Workup

  1. customgiving a solution
  2. temperatureAfter cooling to room temperature
  3. extractionthe mixture is extracted with ethyl acetate (60 ml)
  4. customAfter separation
  5. washthe organic phase is washed with a little hydrochloric acid (1.0 M, 5 ml)
  6. extractionThe aqueous phase is extracted three times with ethyl acetate (60 ml each time)
  7. dry with materialThe combined organic phases are dried over Na2SO4
  8. filtrationfiltered with suction
  9. customevaporated to dryness in vacuo
  10. customThe residue is purified by chromatography over flash silica gel (solvent cyclohexane/ethyl acetate 2:1, parts by volume)

Sources & evidence

ORD record
ord-d391347802cc4565af44e13452c0eef4
Source dataset
uspto-grants-2014_08
Patent number
US08802712B2

Reaction notes

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