Iodine → HCID 20366905, compound

HRID 617003Notes

Reaction equation

HRID 617003 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1[CH:4]=[C:5](Br)[CH:6]=[CH:7][C:8]=1[Cl:9].[Mg].II.[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2([C:36]3[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=3)[CH2:28][CH2:27][CH:26]([N:29]3[CH2:34][CH2:33][C:32](=[O:35])[CH2:31][CH2:30]3)[CH:25]=[CH:24]2)=[CH:19][CH:18]=1.[Cl-].[NH4+]>O1CCCC1>[ClH:9].[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2([C:36]3[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=3)[CH2:28][CH2:27][CH:26]([N:29]3[CH2:34][CH2:33][C:32]([C:5]4[CH:6]=[CH:7][C:8]([Cl:9])=[C:3]([C:2]([F:12])([F:11])[F:1])[CH:4]=4)([OH:35])[CH2:31][CH2:30]3)[CH:25]=[CH:24]2)=[CH:19][CH:18]=1

Participants

7

Reactant 5

HCID 807IodineHCID 25517Ammonium ChlorideHCID 679594-Bromo-2-chloro-alpha,alpha,alpha-trifluorotolueneHCID 5462224MagnesiumHCID 133641271-(1~4~,3~4~-Difluoro[2~3~,2~4~-dihydro-2~2~H-[1~1~,2~1~:2~1~,3~1~-terphenyl]]-2~4~-yl)piperidin-4-one

Product 1

HCID 20366905HCID 20366905, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 6.3 g of 3-trifluoromethyl-4-chloro-1-bromobenzene in 16 ml of tetrahydrofuran is added dropwise to a mixture of 0.6 g of magnesium turnings, a few crystals of iodine and 5 ml of tetrahydrofuran at room temperature with stirring by occasional cooling. After refluxing for 30 minutes, to the cooled Grignard reagent is added dropwise a solution of 7.3 g of 1-[4,4-bis(p-fluorophenyl)-2-cyclohexenyl]-4-piperidone (m.p. 112°-114° C) in 25 ml of tetrahydrofuran by occasional cooling. After the addition is complete, the resulting mixture is stirred at room temperature for 1 hour and then under reflux for an additional hour. After cooling a saturated aqueous solution of ammonium chloride is added dropwise to the reaction mixture, and the whole is extracted with ethyl acetate. The extract is washed with water and dried over sodium sulfate, and the solvent is removed. The residual oil is dissolved in acetone. To the acetone solution is added 20% ethanolic hydrochloric acid, and the whole is cooled. The precipitated crystals are collected by filtration and recrystallized from a mixture of methanol and acetone to give 1-[4,4-bis(p-fluorophenyl)-2-cyclohexenyl]-4-(4-chloro-3-trifluoromethylphenyl)-4-piperidinol hydrochloride as white crystals, melting at 252°-254° C.

Workup

  1. additionAfter the addition
  2. temperatureunder reflux for an additional hour
  3. additionis added dropwise to the reaction mixture
  4. extractionthe whole is extracted with ethyl acetate
  5. washThe extract is washed with water
  6. dry with materialdried over sodium sulfate
  7. customthe solvent is removed
  8. dissolutionThe residual oil is dissolved in acetone
  9. additionTo the acetone solution is added 20% ethanolic hydrochloric acid
  10. temperaturethe whole is cooled
  11. filtrationThe precipitated crystals are collected by filtration
  12. customrecrystallized from a mixture of methanol and acetone

Sources & evidence

ORD record
ord-882096aea8974c2896671d9ad2becca1
Source dataset
uspto-grants-1978_02
Patent number
US04076821

Reaction notes

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