Potassium Hydroxide → 7-[4-Nitro-3-(trifluoromethyl)phenyl]-7-azabicyclo[2.2.1]heptane

HRID 400985Notes

Reaction equation

HRID 400985 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([C:11]([F:14])([F:13])[F:12])[CH:3]=1.[OH-].[K+].Cl.[CH:18]12[NH:24][CH:21]([CH2:22][CH2:23]1)[CH2:20][CH2:19]2>C(Cl)Cl.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([N:24]2[CH:18]3[CH2:23][CH2:22][CH:21]2[CH2:20][CH2:19]3)=[CH:3][C:4]=1[C:11]([F:14])([F:13])[F:12])([O-:10])=[O:9]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 2230945-Fluoro-2-nitrobenzotrifluorideHCID 162795037-Azabicyclo[2.2.1]heptane hydrochloride

Product 1

HCID 575168437-[4-Nitro-3-(trifluoromethyl)phenyl]-7-azabicyclo[2.2.1]heptane

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6344DichloromethaneSolvent

Procedure

To 4-fluoro-1-nitro-2-(trifluoromethyl)benzene (8) dissolved in 3 vol DCM, tetrabutylammoniumbromide (0.05 eq) and 50 wt % KOH (3.6 eq) were added. 7-azabicyclo[2.2.1]heptane hydrochloride (9) was then added at 0-5° C. The reaction was warmed to ambient temperature. The reaction was monitored by HPLC, and when the substrate was <1% AUC, the reaction was considered complete, and the layers are separated. The organic layer was washed with 1M HCl, and the aqueous layer was discarded. The organic layer was then washed once with water, once with brine, and evaporated. The resulting material was recrystallized from cyclohexane at reflux. The solid was filtered, washed with cyclohexane, and dried in a vacuum oven at 45° C. under a nitrogen atmosphere to provide 7-[4-nitro-3-(trifluoromethyl)phenyl]-7-azabicyclo[2.2.1]heptane.

Workup

  1. additionwere added
  2. customthe layers are separated
  3. washThe organic layer was washed with 1M HCl
  4. washThe organic layer was then washed once with water, once with brine
  5. customevaporated
  6. customThe resulting material was recrystallized from cyclohexane
  7. temperatureat reflux
  8. filtrationThe solid was filtered
  9. washwashed with cyclohexane
  10. customdried in a vacuum oven at 45° C. under a nitrogen atmosphere

Sources & evidence

ORD record
ord-b3cf2354852146dda3651cdac96c7c20
Source dataset
uspto-grants-2014_06
Patent number
US08741922B2

Reaction notes

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