Ammonium Chloride → HCID 178444433, compound

HRID 989576Notes

Reaction equation

HRID 989576 reaction equation
[Mg].[F:2][C:3]1[C:8]([F:9])=[CH:7][CH:6]=[CH:5][C:4]=1Br.[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:9][C:8]1[CH:7]=[CH:6][CH:5]=[C:4]([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)[C:3]=1[F:2]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 27332601-Bromo-2,3-difluorobenzeneHCID 5462224MagnesiumHCID 178444451HCID 178444451, compound

Product 1

HCID 178444433HCID 178444433, compoundYield 66.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
50 °C

Procedure

Under nitrogen gas stream, 52.3 g (2150 mmol) of magnesium was added in 100 ml of THF, and a solution of 378 g (1960 mmol) of 2,3-difluoro-1-bromobenzene in 4.0 l of THF was added by drops thereto so that the reaction temperature was maintained at about 50° C. Further, after stirred at room temperature for 1 hour, a solution of 500 g (1630 mmol) of 4-(4-(trans-4-pentylcyclohexyl)butyl)cyclohexanone in 5.0 l of THF was added by drops to the solution and stirred at 50 to 60° C. for 2 hours, and then 1.0 l of saturated aqueous ammonium chloride solution was added to the solution to terminate the reaction. The reaction mixture was filtered with Celite, the solvent was distilled off under a reduced pressure, and then it was extracted with 2.0 l of toluene. The organic layer was washed with 1.0 l of water thrice and dried over anhydrous magnesium sulfate. After the anhydrous magnesium sulfate was removed by filtration, 23.7 g of p-toluenesulfonic acid monohydrate was added to the filtrate and heated to reflux for 4 hours. The organic layer was washed with 1.0 l of water thrice and dried over anhydrous magnesium sulfate. The solvent was distilled off under a reduced pressure, and the residue was subjected to silica gel column chromatography (eluent: heptane) to obtain 436 g of a crude 1,2-difluoro-3-(4-(4-(trans-4-pentylcyclohexyl)-butyl)cyclohexene-1-yl)benzene.

Workup

  1. stirringstirred at 50 to 60° C. for 2 hours
  2. customto terminate
  3. customthe reaction
  4. filtrationThe reaction mixture was filtered with Celite
  5. distillationthe solvent was distilled off under a reduced pressure
  6. extractionit was extracted with 2.0 l of toluene
  7. washThe organic layer was washed with 1.0 l of water thrice
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customAfter the anhydrous magnesium sulfate was removed by filtration, 23.7 g of p-toluenesulfonic acid monohydrate
  10. additionwas added to the filtrate
  11. temperatureheated
  12. temperatureto reflux for 4 hours
  13. washThe organic layer was washed with 1.0 l of water thrice
  14. dry with materialdried over anhydrous magnesium sulfate
  15. distillationThe solvent was distilled off under a reduced pressure

Sources & evidence

ORD record
ord-e09118021f8840949d44bc2d42e316e8
Source dataset
uspto-grants-2002_10
Patent number
US06458433B1

Reaction notes

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