Hydrochloric Acid → 7-Methoxy-4-methylquinoline

HRID 1169666Notes

Reaction equation

HRID 1169666 reaction equation
[C:1]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl-].[Li+].C[Sn](C)(C)C.Br[C:28]1[C:37]2[C:32](=[CH:33][C:34]([O:38][CH3:39])=[CH:35][CH:36]=2)[N:31]=[CH:30][CH:29]=1.Cl.[OH-].[Na+]>CN(C=O)C.CCOC(C)=O.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][C:28]1[C:37]2[C:32](=[CH:33][C:34]([O:38][CH3:39])=[CH:35][CH:36]=2)[N:31]=[CH:30][CH:29]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 11661TetramethyltinHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 433294Lithium ChlorideHCID 215682924-Bromo-7-methoxyquinoline

Product 1

HCID 136855517-Methoxy-4-methylquinolineYield 102.2%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
120 °C

Procedure

4 g of triphenylphosphine, 5.3 g of lithium chloride, 14 ml of tetramethyltin and 2.1 g of bis(triphenylphosphine)palladium(II) chloride are added to a solution of 6 g of 4-bromo-7-methoxyquinoline in 100 ml of DMF, under an inert atmosphere of argon at a temperature in the region of 20° C. The reaction medium is heated at a temperature in the region of 120° C. for 16 hours. After cooling, the insoluble material is filtered off. The filtrate is concentrated under reduced pressure. The residue obtained is taken up in 300 ml of EtOAc and 300 ml of water. After separation of the phases by settling, the organic phase is dried over magnesium sulfate, filtered and then concentrated under reduced pressure. The oil obtained is taken up in 300 ml of EtOAc and 300 ml of water and then acidified with hydrochloric acid to pH 1. The aqueous phase is basified with sodium hydroxide to pH 10 and then extracted with 300 ml of EtOAc. After separation of the phases by settling, the organic phase is dried over magnesium sulfate, filtered and then concentrated under reduced pressure to give 2.7 g of 4-methyl-7-methoxyquinoline, the characteristics of which product are as follows:

Workup

  1. temperatureAfter cooling
  2. filtrationthe insoluble material is filtered off
  3. concentrationThe filtrate is concentrated under reduced pressure
  4. customThe residue obtained
  5. customAfter separation of the phases
  6. dry with materialthe organic phase is dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe oil obtained
  10. extractionextracted with 300 ml of EtOAc
  11. customAfter separation of the phases
  12. dry with materialthe organic phase is dried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2555c3a3c9884e54b3de2e6d927b3cdf
Source dataset
uspto-grants-2010_11
Patent number
US07825115B2

Reaction notes

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