Ammonium Chloride → HCID 178444436, compound

HRID 566163Notes

Reaction equation

HRID 566163 reaction equation
[Mg].[F:2][C:3]1[CH:4]=[C:5](Br)[CH:6]=[C:7]([F:9])[CH:8]=1.[CH2:11]([C@H:16]1[CH2:21][CH2:20][C@H:19]([CH2:22][CH2:23][CH2:24][CH2:25][CH:26]2[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]2)[CH2:18][CH2:17]1)[CH2:12][CH2:13][CH2:14][CH3:15].[Cl-].[NH4+]>C1COCC1>[F:2][C:3]1[CH:4]=[C:5]([C:29]2[CH2:30][CH2:31][CH:26]([CH2:25][CH2:24][CH2:23][CH2:22][C@H:19]3[CH2:18][CH2:17][C@H:16]([CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH2:21][CH2:20]3)[CH2:27][CH:28]=2)[CH:6]=[C:7]([F:9])[CH:8]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 1363131-Bromo-3,5-difluorobenzeneHCID 5462224MagnesiumHCID 178444451HCID 178444451, compound

Product 1

HCID 178444436HCID 178444436, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
50 °C

Procedure

Under a nitrogen gas stream, 3.13 g (129 mmol) of magnesium was added to 50 ml of THF, and while a reaction temperature was maintained at about 50° C., 300 ml of THF containing 22.7 g (118 mmol) of 3,5-difluoro-1-bromobenzene was added dropwise. After stirring for 1 hour at room temperature, 300 ml of THF containing 30.0 g (97.9 mmol) of 4-(4-(trans-4-pentylcyclohexyl)butyl)cyclohexanone was added dropwise. Next, after stirring at 50 to 60° C. for 2 hours, 200 ml of an aqueous saturated ammonium chloride solution was added, thereby terminating the reaction. The reaction mixture was filtered through Celite, and the solvent was then distilled off under reduced pressure, followed by extraction with 500 ml of toluene. The resulting organic layer was washed 3 times with 200 ml of water, and then dried over anhydrous magnesium sulfate. After drying, 1.50 g of p-toluenesulfonic acid monohydrate was added, and heating was done under reflux for 4 hours. The organic layer was washed 3 times with 200 ml of water, and then dried over anhydrous magnesium sulfate. Next, the solvent was distilled off under reduced pressure, and the resulting residue was purified through silica gel column chromatography (a developing solvent: heptane) to obtain 26.4 g of crude 1,3-difluoro-5-(4-(4-(trans-4-pentylcyclohexyl)butyl)cyclohexene-1-yl)benzene.

Workup

  1. stirringNext, after stirring at 50 to 60° C. for 2 hours
  2. customterminating
  3. customthe reaction
  4. filtrationThe reaction mixture was filtered through Celite
  5. distillationthe solvent was then distilled off under reduced pressure
  6. extractionfollowed by extraction with 500 ml of toluene
  7. washThe resulting organic layer was washed 3 times with 200 ml of water
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customAfter drying
  10. addition1.50 g of p-toluenesulfonic acid monohydrate was added
  11. temperatureheating
  12. temperatureunder reflux for 4 hours
  13. washThe organic layer was washed 3 times with 200 ml of water
  14. dry with materialdried over anhydrous magnesium sulfate
  15. distillationNext, the solvent was distilled off under reduced pressure
  16. customthe resulting residue was purified through silica gel column chromatography (a developing solvent

Sources & evidence

ORD record
ord-d193e52584414f1fb67f369683d62a95
Source dataset
uspto-grants-2001_01
Patent number
US06174459B1

Reaction notes

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