Ammonium Chloride → HCID 9968582, compound

HRID 2244490Notes

Reaction equation

HRID 2244490 reaction equation
[CH3:1][N:2]([CH3:18])[C:3]1([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])[CH2:8][CH2:7][C:6](=[O:9])[CH2:5][CH2:4]1.[Cl-:19].[NH4+]>O1CCCC1.C([Mg]Cl)CC1C=CC=CC=1>[CH3:18][N:2]([CH3:1])[C:3]1([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])[CH2:8][CH2:7][C:6]([CH2:11][CH2:10][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)([OH:9])[CH2:5][CH2:4]1.[ClH:19].[CH3:18][N:2]([CH3:1])[C:3]1([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])[CH2:8][CH2:7][C:6]([CH2:11][CH2:10][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)([OH:9])[CH2:5][CH2:4]1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 68550651HCID 68550651, compound

Product 2

HCID 9968582HCID 9968582, compoundHCID 10200497HCID 10200497, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 178418865HCID 178418865, compoundSolvent

Procedure

5.79 g 4-dimethylamino-4-(2-fluorobenzyl)cyclohexanone were dissolved in 35 ml analytical grade tetrahydrofuran, 42 ml 1.0 molar phenethylmagnesium chloride solution in THF were added under a nitrogen atmosphere, while cooling in an ice-bath, and the mixture was stirred overnight at room temperature. For working up, 42 ml ammonium chloride solution (20 per cent by weight) were added, while cooling with ice, the phases were separated, the aqueous phase was extracted three times with 50 ml diethyl ether each time, the combined organic phases were washed with 30 ml water and extracted three times with 50 ml dilute hydrochloric acid (5 per cent by weight) each time, the combined aqueous extracts were washed with 50 ml diethyl ether, adjusted to pH 9 with ammonia solution (25 per cent by weight) and extracted three times with 50 ml methylene chloride each time, the combined methylene chloride extracts were dried over sodium sulfate, filtered and concentrated and the residue was largely freed from solvent residues in vacuo. The crude product obtained (7.76 g) was chromatographed over silica gel with diethyl ether/hexane (v/v=1:1). 1.33 g of the nonpolar diastereoisomer of 4-dimethylamino-4-(2-fluorobenzyl)-1-phenethylcyclohexanol were obtained, from which 536 mg of the corresponding hydrochloride were prepared as described for example 4.

Workup

  1. additionwere added under a nitrogen atmosphere
  2. temperaturewhile cooling in an ice-bath
  3. temperaturewhile cooling with ice
  4. customthe phases were separated
  5. extractionthe aqueous phase was extracted three times with 50 ml diethyl ether each time
  6. washthe combined organic phases were washed with 30 ml water
  7. extractionextracted three times with 50 ml dilute hydrochloric acid (5 per cent by weight) each time
  8. washthe combined aqueous extracts were washed with 50 ml diethyl ether
  9. extractionextracted three times with 50 ml methylene chloride each time
  10. dry with materialthe combined methylene chloride extracts were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude product obtained (7.76 g)
  14. customwas chromatographed over silica gel with diethyl ether/hexane (v/v=1:1)

Sources & evidence

ORD record
ord-85a35d2340c441b582f85ffbd5e26a7d
Source dataset
uspto-grants-2010_03
Patent number
US07678834B2

Reaction notes

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