Hydrochloric Acid → HCID 86735314, compound

HRID 1448561Notes

Reaction equation

HRID 1448561 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5](Br)[CH:6]=[CH:7][CH:8]=1.[Mg].[CH2:13]1[O:27][C:16]2([CH2:21][CH2:20][C:19](C#N)([N:22]([CH3:24])[CH3:23])[CH2:18][CH2:17]2)[O:15][CH2:14]1.[Cl-:28].[NH4+].Cl>C(OCC)C.C(Cl)Cl.C1C=CC=CC=1.O1CCCC1>[ClH:28].[CH2:14]1[O:15][C:16]2([CH2:21][CH2:20][C:19]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:11])([F:10])[F:1])[CH:4]=3)([N:22]([CH3:23])[CH3:24])[CH2:18][CH2:17]2)[O:27][CH2:13]1

Participants

10

Reactant 5

HCID 313Hydrochloric Acid2×HCID 9817Benzene, 1-bromo-3-(trifluoromethyl)-HCID 25517Ammonium ChlorideHCID 3609778-(Dimethylamino)-1,4-dioxaspiro[4.5]decane-8-carbonitrileHCID 5462224Magnesium

Product 1

HCID 86735314HCID 86735314, compoundYield 24%

Reagents, catalysts & solvents 4

HCID 241BenzeneSolventHCID 3283Diethyl EtherSolvent3×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A Grignard reagent is prepared using 4.79 gm. (0.024 mole) m-trifluoromethylbromobenzene, 0.59 gm. magnesium and 50 ml. tetrahydrofuran; to this is added 1.50 gm. (0.0071 mole) 4-cyano-4-dimethylaminocyclohexanone ethylene ketal (prepared in Example 41, Part B, dissolved in 40 ml. tetrahydrofuran. This reaction mixture is heated at the reflux temperature for 17 hours. It is then cooled, chilled in ice, and 20 ml. saturated aqueous ammonium chloride and benzene are added. The organic solution is then separated, initially washed with water, and then washed with brine. The solvents are then removed by evaporation under reduced pressure. The residue thus obtained is dissolved in diethyl ether, and 4 N ethereal hydrogen chloride is added until precipitation of the hydrochloride salt as a gum is complete. The supernatant liquid is decanted and the remaining gum is dissolved in methylene chloride. One N aqueous sodium hydroxide is added. The organic layer is then separated and the methylene chloride is removed by evaporation under reduced pressure. The residue thus obtained is transferred onto a 200 ml. column of silica gel and the chromatogram is developed with methylene chloride containing 3% metahnol. The appropriate fractions, as determined by TLC, are collected and combined. The solvent is removed by evaporation under reduced pressure, and the gummy residue thus obtained is dissolved in diethyl ether. The ether solution is treated with 4 N ethereal hydrogen chloride until precipitation of the hydrochloride salt is complete. The precipitate is collected on a filter and then recrystallized from a mixture of methylene chloride and ethyl acetate to give 0.63 gm. (24% yield) of 4-(m-trifluoromethylphenyl)-4-dimethylaminocyclohexanone ethylene ketal hydrochloride having a melting point at 231° to 232° C.

Workup

  1. additionto this is added 1.50 gm
  2. dissolutiondissolved in 40 ml
  3. temperatureThis reaction mixture is heated at the reflux temperature for 17 hours
  4. temperatureIt is then cooled
  5. temperaturechilled in ice
  6. customThe organic solution is then separated
  7. washinitially washed with water
  8. washwashed with brine
  9. customThe solvents are then removed by evaporation under reduced pressure
  10. customThe residue thus obtained
  11. customThe supernatant liquid is decanted
  12. dissolutionthe remaining gum is dissolved in methylene chloride
  13. additionOne N aqueous sodium hydroxide is added
  14. customThe organic layer is then separated
  15. customthe methylene chloride is removed by evaporation under reduced pressure
  16. customThe residue thus obtained
  17. customare collected
  18. customThe solvent is removed by evaporation under reduced pressure
  19. customthe gummy residue thus obtained
  20. customThe precipitate is collected on
  21. filtrationa filter
  22. customrecrystallized from a mixture of methylene chloride and ethyl acetate
  23. customto give 0.63 gm

Sources & evidence

ORD record
ord-082b9da44c4f4934ac1362bf6c41cb6a
Source dataset
uspto-grants-1979_12
Patent number
US04180584

Reaction notes

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