Hydrochloric Acid → 1-(2-Fluoropyridin-4-yl)-2-(4-fluorophenyl)ethane-1,2-dione-1-oxime

HRID 23520Notes

Reaction equation

HRID 23520 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:17])[CH2:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([F:16])[CH:11]=2)=[CH:4][CH:3]=1.C([O:22][N:23]=O)(C)(C)C.Cl>C(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:17])[C:9]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([F:16])[CH:11]=2)=[N:23][OH:22])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 10906Tert-Butyl nitriteHCID 110317691-(4-Fluorophenyl)-2-(2-fluoropyridin-4-yl)ethanone

Product 1

HCID 1363357801-(2-Fluoropyridin-4-yl)-2-(4-fluorophenyl)ethane-1,2-dione-1-oxime

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
-5 °C

Procedure

To a solution of 1-(4-fluorophenyl)-2-(2-fluoropyridin-4-yl)ethanone (43 g, 0.184 mol) in ethanol (800 mL) at −10° C. was added dropwise t-butylnitrite (24.1 mL, 0.20 mol) over 10 minutes followed by 2.5 M HCl in absolute ethanol (60 mL, 0.15 mol). The reaction temperature was maintained at −5° C. during these additions. After addition was complete, the dry ice bath was removed and the reaction was allowed to warm to RT and stirred overnight. The ethanol was removed under reduced pressure and the residue was diluted with H2O and made basic with saturated NaHCO3. It was extracted with EtOAc, the combined organic extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The crude residue was taken up in methanol/isopropanol and mixed with toluene. The methanol/isopropanol mixture was concentrated under reduced pressure and the title compound was recrystallized from hexane/toluene (47.5 g).

Workup

  1. additionAfter addition
  2. customthe dry ice bath was removed
  3. temperatureto warm to RT
  4. customThe ethanol was removed under reduced pressure
  5. additionthe residue was diluted with H2O
  6. extractionIt was extracted with EtOAc
  7. washthe combined organic extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. additionmixed with toluene
  11. concentrationThe methanol/isopropanol mixture was concentrated under reduced pressure
  12. customthe title compound was recrystallized from hexane/toluene (47.5 g)

Sources & evidence

ORD record
ord-1d06d0ff4d014949935a5779baef892a
Source dataset
uspto-grants-2005_02
Patent number
US06852727B2

Reaction notes

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