Iodine → 3-Fluoro-4-iodoquinoline

HRID 395006Notes

Reaction equation

HRID 395006 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:15]=[N:16][C:17]2[C:22]([CH:23]=1)=[CH:21][CH:20]=[CH:19][CH:18]=2.[I:24]I.[Cl-].[Na+]>O1CCCC1.CCCCCC.C(OCC)(=O)C.O1CCCC1.O>[F:13][C:14]1[CH:15]=[N:16][C:17]2[C:22]([C:23]=1[I:24])=[CH:21][CH:20]=[CH:19][CH:18]=2

Participants

10

Reactant 5

HCID 807IodineHCID 5234Sodium ChlorideHCID 7912DiisopropylamineHCID 964053-FluoroquinolineHCID 178418339Butyllithium

Product 1

HCID 111084963-Fluoro-4-iodoquinolineYield 68.4%

Reagents, catalysts & solvents 4

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
-70 °C

Procedure

17.3 cm3 of diisopropylamine in 650 cm3 of tetrahydrofuran were cooled to a temperature in the region of −75° C. and 76 cm3 of a 1.6M solution of butyl lithium in hexane were added, with stirring and under an inert atmosphere, while maintaining the temperature at about −70° C. After stirring for 20 minutes at a temperature in the region of −75° C., a solution of 11.9 g of 3-fluoroquinoline in 200 cm3 of tetrahydrofuran was added. The solution obtained was stirred for a further 4 hours at −75° C., followed by addition of a solution of 32.2 g of double-sublimed iodine in 150 cm3 of tetrahydrofuran. After stirring for 2 hours at a temperature in the region of −40° C., the reaction mixture was hydrolyzed with 200 cm3 of a tetrahydrofuran/water mixture (90/10 by volume) and then with 200 cm3 of saturated sodium chloride solution. In the region of 20° C., the mixture was diluted with 300 cm3 of ethyl acetate and washed with twice 250 cm3 of saturated sodium chloride solution. The organic phase was dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 50° C. The residue obtained was purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45μ; diameter 10 cm; height 30 cm), eluting with dichloromethane and collecting 100-cm3 fractions. Fractions 45 to 80 were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 15.1 g of 3-fluoro-4-iodoquinoline were obtained in the form of a cream-colored solid melting at 110° C.

Workup

  1. additionwere added
  2. stirringAfter stirring for 20 minutes at a temperature in the region of −75° C.
  3. customThe solution obtained
  4. stirringwas stirred for a further 4 hours at −75° C.
  5. stirringAfter stirring for 2 hours at a temperature in the region of −40° C.
  6. washwashed with twice 250 cm3 of saturated sodium chloride solution
  7. dry with materialThe organic phase was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 50° C
  10. customThe residue obtained
  11. customwas purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45μ; diameter 10 cm; height 30 cm)
  12. washeluting with dichloromethane
  13. customcollecting 100-cm3 fractions
  14. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-a582f043f0f2446bab3a04525e11a13a
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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