Hydrochloric Acid → 6,7-Difluoro-2-methylquinoline

HRID 326943Notes

Reaction equation

HRID 326943 reaction equation
[CH:1](=O)/[CH:2]=[CH:3]/[CH3:4].[F:6][C:7]1[CH:8]=[C:9]([CH:11]=[CH:12][C:13]=1[F:14])[NH2:10].C1(Cl)C(=O)C(Cl)=C(Cl)C(=O)C=1Cl.Cl>CC(O)CC.C1COCC1>[F:14][C:13]1[CH:12]=[C:11]2[C:9](=[CH:8][C:7]=1[F:6])[N:10]=[C:3]([CH3:4])[CH:2]=[CH:1]2

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8371ChloranilHCID 774693,4-DifluoroanilineHCID 447466Crotonaldehyde

Product 1

HCID 222413776,7-Difluoro-2-methylquinolineYield 57%

Reagents, catalysts & solvents 2

HCID 6568(+-)-2-ButanolSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Crotonaldehyde (226.34 g, 3.23 mol) in 100 mL of 2-butanol was added dropwise to a refluxing solution of 3,4-difluoroaniline (417.27 g, 3.23 mol), p-chloranil (794.65 g, 3.23 mol) and HCl conc. (808 mL) in 5.4 L of 2-butanol. After 2 hours of heating 2.7 L of solvent was removed under vacuum at ca. 60° C. Then 2 L of toluene was added to the reaction mixture followed by removal of 2.5-3 L of solvent until a very pasty solid formed. THF (2 L) was added and the mixture heated 30 min. after which it was cooled to 0° C. The solid was collected and washed with THF until pure by tlc. The solid was then dissolved in aq. K2CO3 /EtOAc and the organic phase separated. The aqueous phase was extracted with EtOAc (2×) and the organic phases combined, dried over MgSO4 and the solvent removed. The product was crystallized in the minimum amount of EtOAc to give 328.08 g (57%) of the title compound.

Workup

  1. customwas removed under vacuum at ca. 60° C
  2. additionThen 2 L of toluene was added to the reaction mixture
  3. customfollowed by removal of 2.5-3 L of solvent until a very pasty solid
  4. customformed
  5. temperaturethe mixture heated 30 min. after which it
  6. customThe solid was collected
  7. washwashed with THF until pure by tlc
  8. dissolutionThe solid was then dissolved in aq. K2CO3 /EtOAc
  9. customthe organic phase separated
  10. extractionThe aqueous phase was extracted with EtOAc (2×)
  11. dry with materialdried over MgSO4
  12. customthe solvent removed
  13. customThe product was crystallized in the minimum amount of EtOAc

Sources & evidence

ORD record
ord-dbdd9894e07c462ba239e885e42eeef5
Source dataset
uspto-grants-1993_12
Patent number
US05270324

Reaction notes

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