Ethyl Acetate → 3-fluoro-6-methoxyquinoline

HRID 747483Notes

Reaction equation

HRID 747483 reaction equation
[F:1][B-](F)(F)F.[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[N:14]=[CH:13][C:12]([N+]#N)=[CH:11]2.C(OCC)(=O)C.[OH-].[Na+]>C1(C)C=CC=CC=1>[F:1][C:12]1[CH:13]=[N:14][C:15]2[C:10]([CH:11]=1)=[CH:9][C:8]([O:7][CH3:6])=[CH:17][CH:16]=2

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 11737373HCID 11737373, compound

Product 1

HCID 113098403-fluoro-6-methoxyquinolineYield 100.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of 1007 g of 6-methoxy-3-quinolinediazonium fluoroborate taken in 9 l of toluene is heated to 60° C. in 85 minutes. A release of gas is observed at 60° C. The reaction medium is then gradually heated further for 90 minutes to 70-72° C. After having been kept at 72° C. for 90 minutes, the medium is then gradually heated again to 85° C. After cooling and stirring overnight, 4 l of ice-cold water are added to the suspension. After having stirred for 15 minutes, 2.5 l of ethyl acetate are added. After having stirred for 45 minutes, the pH is adjusted to pH=7-7.5 by adding 47% sodium hydroxide (250 ml). The medium is stirred for 30 minutes and then separated by settling out for 1 hour. The lower aqueous phase is re-extracted with ethyl acetate. The organic phases are combined together and washed with water. The solution is filtered and then concentrated under reduced pressure so as to give 655 g of crude 3-fluoro-6-methoxyquinoline. The crude product is distilled under reduced pressure. The distillation fractions (bp 103-110° C. under 1 mbar) containing the expected product are combined together. 498.9 g of 3-fluoro-6-methoxyquinoline (76%) are thus obtained in the form of a white solid which melts at 51-53° C.

Workup

  1. customis observed at 60° C
  2. temperatureThe reaction medium is then gradually heated further for 90 minutes to 70-72° C
  3. temperaturethe medium is then gradually heated again to 85° C
  4. temperatureAfter cooling
  5. stirringAfter having stirred for 15 minutes
  6. stirringAfter having stirred for 45 minutes
  7. stirringThe medium is stirred for 30 minutes
  8. customseparated
  9. waitby settling out for 1 hour
  10. extractionThe lower aqueous phase is re-extracted with ethyl acetate
  11. washwashed with water
  12. filtrationThe solution is filtered
  13. concentrationconcentrated under reduced pressure so as

Sources & evidence

ORD record
ord-c0bac5c29e454fdeb06e1e34f414efed
Source dataset
uspto-grants-2008_07
Patent number
US07396934B2

Reaction notes

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