Ammonium Chloride → (1RS,2RS,5SR)-1-(3-benzyloxy-phenyl)-2-dimethylaminomethyl-5-trifluoromethyl-cyclohexanol

HRID 3617Notes

Reaction equation

HRID 3617 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11](Br)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Mg].[CH3:17][N:18]([CH2:20][CH:21]1[CH2:26][CH2:25][CH:24]([C:27]([F:30])([F:29])[F:28])[CH2:23][C:22]1=[O:31])[CH3:19].FC(F)(F)C1CCCC(=O)C1.CN(C(Cl)Cl)C.[Cl-].[NH4+]>O1CCCC1.C(#N)C.CCOCC>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:22]2([OH:31])[CH2:23][CH:24]([C:27]([F:30])([F:29])[F:28])[CH2:25][CH2:26][CH:21]2[CH2:20][N:18]([CH3:17])[CH3:19])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

10

Reactant 6

HCID 25517Ammonium ChlorideHCID 27566381-(Benzyloxy)-3-bromobenzene2×HCID 27793553-(Trifluoromethyl)cyclohexanoneHCID 5462224MagnesiumHCID 10290805Dimethylaminomethylene chlorideHCID 21705850(2RS,5RS)-2-dimethylaminomethyl-5-trifluoromethyl-cyclohexanone

Product 1

HCID 18935039(1RS,2RS,5SR)-1-(3-benzyloxy-phenyl)-2-dimethylaminomethyl-5-trifluoromethyl-cyclohexanol

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

43.9 g (167 mmole) 3-benzyloxy-1-bromobenzene, dissolved in 200 ml of dry tetrahydrofuran, were added drop-wise to 4.06 g (167 mmole) magnesium turnings in 40 ml of dry tetrahydrofuran so that the reaction mixture boiled gently. After the addition of 3-benzyloxy-1-bromobenzene was complete, the mixture was heated for one hour under reflux and was thereafter cooled to 5°-10° C. 30.8 g (139 mmole) (2RS,5SR)-2-dimethylaminomethyl-5-trifluoromethyl-cyclohexanone, prepared from 3-trifluoromethyl-cyclohexanone and dimethylaminomethylene chloride in acetonitrile, dissolved in 80 ml of dry tetrahydrofuran, were added at this temperature. The reaction mixture was allowed to stand overnight and was then cooled to 5°-10° C. again. The Grignard solution was decomposed by the addition of 150 ml of 20% ammonium chloride solution. The reaction mixture was diluted with 200 ml of ether, the organic phase was separated off and the aqueous phase was extracted twice with 100 ml ether. The combined organic phases were dried over sodium sulphate. After removing the solvent by distillation, the residue (60.6 g) was introduced on to an 8×50 cm column packed with silica gel and extracted with ethyl acetate/methanol. 27.8 g (50% theoretical) of base (26) were obtained.

Workup

  1. temperaturethe mixture was heated for one hour
  2. temperatureunder reflux
  3. temperaturewas thereafter cooled to 5°-10° C
  4. additionwere added at this temperature
  5. temperaturewas then cooled to 5°-10° C. again
  6. customthe organic phase was separated off
  7. extractionthe aqueous phase was extracted twice with 100 ml ether
  8. dry with materialThe combined organic phases were dried over sodium sulphate
  9. customAfter removing the solvent
  10. distillationby distillation
  11. additionthe residue (60.6 g) was introduced on to an 8×50 cm column
  12. extractionextracted with ethyl acetate/methanol

Sources & evidence

ORD record
ord-6ddb642f02864792bfbacd5b7be3fb31
Source dataset
uspto-grants-1998_03
Patent number
US05733936

Reaction notes

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