Ammonium Chloride → 4-benzyl-4-dimethylamino-1-phenethylcyclohexanol

HRID 2244482Notes

Reaction equation

HRID 2244482 reaction equation
[CH2:1]([C:8]1([N:15]([CH3:17])[CH3:16])[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[NH4+]>O1CCCC1.C([Mg]Cl)CC1C=CC=CC=1>[CH2:1]([C:8]1([N:15]([CH3:16])[CH3:17])[CH2:9][CH2:10][C:11]([CH2:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)([OH:14])[CH2:12][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 204534784-Benzyl-4-(dimethylamino)cyclohexanone

Product 1

HCID 99514654-benzyl-4-dimethylamino-1-phenethylcyclohexanol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 178418865HCID 178418865, compoundSolvent

Procedure

25.0 g 4-benzyl-4-dimethylaminocyclohexanone were dissolved in 150 ml analytical grade tetrahydrofuran, 151 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, 150 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 80 ml diethyl ether each time, the combined organic phases were extracted three times with 70 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 80 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 (32.6 g) was chromatographed over silica gel with diethyl ether/hexane (v/v=1:1). 3.5 g of the nonpolar diastereoisomer of 4-benzyl-4-dimethylamino-1-phenethylcyclohexanol obtained were dissolved in 28 ml 2-butanone, 103 μl water followed by 1.44 ml trimethylchlorosilane were added at room temperature and the mixture was stirred over night at room temperature. The white solid which had precipitated out was filtered with suction, washed with diethyl ether and dried in an oil pump vacuum. 2.47 g of the hydrochloride of the nonpolar diastereoisomer of 4-benzyl-4-dimethylamino-1-phenethylcyclohexanol were obtained.

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 80 ml diethyl ether each time
  6. extractionthe combined organic phases were extracted three times with 70 ml dilute hydrochloric acid (5 per cent by weight) each time
  7. washthe combined aqueous extracts were washed with 50 ml diethyl ether
  8. extractionextracted three times with 80 ml methylene chloride each time
  9. dry with materialthe combined methylene chloride extracts were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product obtained (32.6 g)
  13. customwas chromatographed over silica gel with diethyl ether/hexane (v/v=1:1)

Sources & evidence

ORD record
ord-1bfd455b6206426e8518492aa687fd61
Source dataset
uspto-grants-2010_03
Patent number
US07678834B2

Reaction notes

Loading…