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

HRID 407142Notes

Reaction equation

HRID 407142 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

4-fluoro-1-nitro-2-(trifluoromethyl)benzene was dissolved in 3 vol DCM. Tetrabutylammoniumbromide (0.05 eq) and KOH (50 wt %, 3.6 eq) were added. 7-azabicyclo[2.2.1]heptane hydrochloride (8-HCl) was then added at 0-5° C. The reaction was warmed up to ambient temperature and monitored by HPLC. Once substantially complete, the layers were separated and the organic layer was washed with 1M HCl. The layers were separated and the aqueous layer was discarded. The organic layer was washed once with water, once with brine, and then distilled. 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. with a N2 gas bleed to provide 7-[4-nitro-3-(trifluoromethyl)phenyl]-7-azabicyclo[2.2.1]heptane (9).

Workup

  1. customOnce substantially complete, the layers were separated
  2. washthe organic layer was washed with 1M HCl
  3. customThe layers were separated
  4. washThe organic layer was washed once with water, once with brine
  5. distillationdistilled
  6. customThe resulting material was recrystallized from cyclohexane
  7. temperatureat reflux
  8. filtrationThe solid was filtered
  9. washwashed with cyclohexane
  10. dry with materialdried in a vacuum oven at 45° C. with a N2 gas

Sources & evidence

ORD record
ord-c72fd0cb57e14adbb1ba5452be6d055f
Source dataset
uspto-grants-2014_06
Patent number
US08754222B2

Reaction notes

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