Hydrochloric Acid → N-[3,5-bis(trifluoromethyl)phenyl]-2,4-dioxobicyclo[3.2.1]octane-3-carboxamide

HRID 349789Notes

Reaction equation

HRID 349789 reaction equation
[CH:1]12[CH2:8][CH:5]([CH2:6][CH2:7]1)[C:4](=[O:9])[CH2:3][C:2]2=[O:10].[F:11][C:12]([F:27])([F:26])[C:13]1[CH:14]=[C:15]([N:23]=[C:24]=[O:25])[CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=1.[H-].[Na+].Cl>CN(C)C=O.O>[F:11][C:12]([F:26])([F:27])[C:13]1[CH:14]=[C:15]([NH:23][C:24]([CH:3]2[C:4](=[O:9])[CH:5]3[CH2:8][CH:1]([CH2:7][CH2:6]3)[C:2]2=[O:10])=[O:25])[CH:16]=[C:17]([C:19]([F:22])([F:20])[F:21])[CH:18]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 144686Bicyclo(3.2.1)octane-2,4-dioneHCID 27333143,5-Bis(trifluoromethyl)phenyl isocyanate

Product 1

HCID 11603558N-[3,5-bis(trifluoromethyl)phenyl]-2,4-dioxobicyclo[3.2.1]octane-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of bicyclo[3,2,1]octane-2,4-dione (0.34 g, 2.5 mmole), 3,5-bis(trifluoromethyl)phenyl isocyanate (0.86 ml, 5.0 mmole), and 60% sodium hydride in mineral oil (0.11 g, 2.75 mmole) in dimethylformamide (100 mL) was stirred at 0° C. for 1 hour and heated at 45–50° C. under nitrogen for 24 hours. After cooling, the mixture was diluted with H2O and treated with 2N aqueous HCl until the mixture was clear. The clear solution was then extracted with dichloromethane. The organic layer was washed with H2O again, dried over anhydrous magnesium sulfate, and concentrated on a rotary evaporator. The residue was purified by chromatography on silica gel (30% dichloromethane/hexane) to give a clear oil as the expected product. The oily product was crystallized by triturated with hexane in a dry ice bath and collected at room temperature to give the title compound as a white solid, mp=88–90° C.; (−) ESI m/z=392 (M−H)−.

Workup

  1. temperatureheated at 45–50° C. under nitrogen for 24 hours
  2. temperatureAfter cooling
  3. extractionThe clear solution was then extracted with dichloromethane
  4. washThe organic layer was washed with H2O again
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated on a rotary evaporator
  7. customThe residue was purified by chromatography on silica gel (30% dichloromethane/hexane)

Sources & evidence

ORD record
ord-ed791cb55edc45dcb6378ec25a4293e5
Source dataset
uspto-grants-2007_02
Patent number
US07179943B2

Reaction notes

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