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

HRID 1755773노트

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HRID 1755773 반응식
[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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 6568(+-)-2-Butanol용매2회HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

Crotonaldehyde (226.34 g, 3.23 tool) in 100 mL of 2-butanol was added dropwise to a refluxing solution of 3,4-difluoroaniline (417.27 g, 3.23 tool), 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 (2L) 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 (2X) 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.

후처리

  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 (2X)
  11. dry with materialdried over MgSO4
  12. customthe solvent removed
  13. customThe product was crystallized in the minimum amount of EtOAc

출처 및 근거

ORD 기록
ord-46f6a75ffc5b4c08b4966f3172315ff7
출처 데이터셋
uspto-grants-1995_08
특허 번호
US05438141

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