1,2-Dichlorobenzene → 3-fluoro-6-methoxyquinoline

HRID 2421523Notes

Reaction equation

HRID 2421523 reaction equation
B(F)(F)[F:2].CCOCC.N[C:11]1[CH:12]=[N:13][C:14]2[C:19]([CH:20]=1)=[CH:18][C:17]([O:21][CH3:22])=[CH:16][CH:15]=2.C(ON=O)(C)(C)C.ClC1C=CC=CC=1Cl>ClCCl.CCCCCC.C(OCC)(=O)C>[F:2][C:11]1[CH:12]=[N:13][C:14]2[C:19]([CH:20]=1)=[CH:18][C:17]([O:21][CH3:22])=[CH:16][CH:15]=2

Participants

7

Reactant 4

HCID 72391,2-DichlorobenzeneHCID 8000Boron trifluoride etherateHCID 10906Tert-Butyl nitriteHCID 5999396-Methoxyquinolin-3-amine

Product 1

HCID 113098403-fluoro-6-methoxyquinoline

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent4×HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
73 °C

Procedure

To boron trifluoride etherate (1.29 g) at −12° C. under an atmosphere of nitrogen was added with stirring a solution of 3-amino-6-methoxyquinoline (1.05 g) in dry dichloromethane (15 ml). The yellow suspension was stirred for 15 minutes then a solution of t-butylnitrite (0.74 g) in dichloromethane (5 ml) was added dropwise. The mixture was stirred for 2 hours at 0° C. then 1,2-dichlorobenzene was added and the mixture gradually heated to 73° C., allowing the dichloromethane to distil out from the reaction vessel and then increased to 90° C. to complete the reaction. The mixture was allowed to cool to ambient temperature, diluted with dichloromethane, washed with water, dried over magnesium sulfate, filtered then evaporated under reduced pressure to give a black oil that was fractionated by chromatography (silica; hexane/ethyl acetate) to give an oil, 0.54 g, containing the required product. MH+178

Workup

  1. stirringThe mixture was stirred for 2 hours at 0° C.
  2. customto distil out from the reaction vessel
  3. temperatureincreased to 90° C.
  4. customthe reaction
  5. temperatureto cool to ambient temperature
  6. washwashed with water
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customthen evaporated under reduced pressure
  10. customto give a black oil that
  11. customto give an oil, 0.54 g

Sources & evidence

ORD record
ord-9e30deeb702c45d1871492d9cb7753af
Source dataset
uspto-grants-2011_06
Patent number
US07956188B2

Reaction notes

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