Hydrochloric Acid → 3-Iodo-8-(4-methyl-piperazin-1-yl)-quinoline

HRID 1010586Notes

Reaction equation

HRID 1010586 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][C:6]=2[N:12]1[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]1.[I-:19].[K+].C1(C)C=CC=CC=1.Cl>CN(C)P(N(C)C)(N(C)C)=O.[Cu]I>[I:19][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][C:6]=2[N:12]1[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 4875Potassium IodideHCID 673136243-Bromo-8-(4-methyl-piperazin-1-yl)-quinoline

Product 1

HCID 673137463-Iodo-8-(4-methyl-piperazin-1-yl)-quinoline

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 3-bromo-8-(4-methyl-piperazin-1-yl)-quinoline (D1)(1.75 g, 5.7 mmol), copper (I) iodide (5.4 g, 28.5 mmol) and potassium iodide (9.6 g, 57.8 mmol) in hexamethylphosphoramide (20 ml) was heated in an oil bath at 150° C. for 21 h under argon. To the cooled reaction mixture was added toluene (120 ml) and 1M hydrochloric acid (120 ml) and the whole was shaken vigorously for 5 minutes. The insoluble brown solid was then collected by filtration, washed with methanol (3×40 ml) and resuspended in a mixture of dichloromethane (150 ml) and 2M sodium hydroxide (150 ml). After shaking the mixture vigorously, the insoluble material was filtered, washed with dichloromethane (2×50 ml) and discarded. The filtrate and washings were transferred to a separating funnel and the layers were separated. The aqueous phase was extracted with dichloromethane (2×100 ml) and the combined organic extracts were dried (MgSO4) and concentrated to a brown oil (1.5 g) which was identified by NMR spectroscopy as a mixture of the title compound (D2) and 3-bromo-8-(4-methyl-piperazin-1-yl)-quinoline (D1) in a ratio of 4:1. This mixture was used directly in the next stage (see Example 1).

Workup

  1. customTo the cooled reaction mixture
  2. filtrationThe insoluble brown solid was then collected by filtration
  3. washwashed with methanol (3×40 ml)
  4. additionresuspended in a mixture of dichloromethane (150 ml) and 2M sodium hydroxide (150 ml)
  5. stirringAfter shaking the mixture vigorously
  6. filtrationthe insoluble material was filtered
  7. washwashed with dichloromethane (2×50 ml)
  8. customThe filtrate and washings were transferred to a separating funnel
  9. customthe layers were separated
  10. extractionThe aqueous phase was extracted with dichloromethane (2×100 ml)
  11. dry with materialthe combined organic extracts were dried (MgSO4)
  12. concentrationconcentrated to a brown oil (1.5 g) which
  13. additionwas identified by NMR spectroscopy as a mixture of the title compound (D2) and 3-bromo-8-(4-methyl-piperazin-1-yl)-quinoline (D1) in a ratio of 4:1

Sources & evidence

ORD record
ord-552dd4385299406595d5ccaad912a7e9
Source dataset
uspto-grants-2011_07
Patent number
US07977337B2

Reaction notes

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