1-[2-(3-Methoxyphenyl)cyclohexyl]-N,N-dimethylmethanamine → Phenol, 3-[2-[(dimethylamino)methyl]cyclohexyl]-

HRID 557504Notes

Reaction equation

HRID 557504 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]([CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]2[CH2:15][N:16]([CH3:18])[CH3:17])[CH:6]=[CH:7][CH:8]=1>Br>[CH3:18][N:16]([CH2:15][CH:10]1[CH2:11][CH2:12][CH2:13][CH2:14][CH:9]1[C:5]1[CH:4]=[C:3]([OH:2])[CH:8]=[CH:7][CH:6]=1)[CH3:17]

Participants

3

Reactant 1

HCID 30565771-[2-(3-Methoxyphenyl)cyclohexyl]-N,N-dimethylmethanamine

Product 1

HCID 10059894Phenol, 3-[2-[(dimethylamino)methyl]cyclohexyl]-

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Procedure

125 g (440 mmole) of the precursor 1-(2-(3-methoxyphenyl)cyclohexyl)-N,N-dimethylmethaneamine and 500 ml of hydrobromic acid (47%, in water) were introduced together into a single necked flask and stirred under reflux for 2 hours using a magnetic stirrer. After conclusion of the reaction, the hydrogen bromide was distilled off by applying a vacuum (water-jet pump). The distillation residue was added to 250 ml water, and the suspension was covered with a layer of 1000 ml ethyl acetate. The pH of the reaction mixture was adjusted to pH 8 with aqueous sodium-hydroxide solution (c=32% w/w), accompanied by cooling of the reaction mixture with ice. Organic and aqueous phases were separated, the aqueous phase was extracted three times with 350 ml portions of ethyl acetate. In the process, the pH value was monitored and maintained at a value of at least pH 8 using aqueous sodium-hydroxide solution (c=32% w/w). The mixture was extracted two more times with 150 ml portions of ethyl acetate, and the organic phase was dried with MgSO4. The solvent was removed in a rotary evaporator (bath temperature 44° C., vacuum <20 mbar). The yield of crude product 3-[2-(dimethylamino)methyl(cyclohex-1-yl)]phenol amounted to 101 g. The crude product 3-[2-(dimethylamino)methyl(cyclohex-1-yl)]phenol was added to 100 ml acetone and stirred until the light-brown material solidified. Subsequently the material was filtered out by suction and washed with a little diethyl ether. The yield amounted to 48%, relative to the quantity of crude product employed.

Workup

  1. temperatureunder reflux for 2 hours
  2. customAfter conclusion of the reaction
  3. distillationthe hydrogen bromide was distilled off
  4. additionThe distillation residue was added to 250 ml water
  5. temperatureby cooling of the reaction mixture with ice
  6. customOrganic and aqueous phases were separated
  7. extractionthe aqueous phase was extracted three times with 350 ml portions of ethyl acetate
  8. temperaturemaintained at a value of at least pH 8
  9. extractionThe mixture was extracted two more times with 150 ml portions of ethyl acetate
  10. dry with materialthe organic phase was dried with MgSO4
  11. customThe solvent was removed in a rotary evaporator (bath temperature 44° C., vacuum <20 mbar)
  12. additionThe crude product 3-[2-(dimethylamino)methyl(cyclohex-1-yl)]phenol was added to 100 ml acetone
  13. stirringstirred until the light-brown material
  14. filtrationSubsequently the material was filtered out by suction
  15. washwashed with a little diethyl ether

Sources & evidence

ORD record
ord-c962013b6c904464919222b2dbdabc15
Source dataset
uspto-grants-2011_11
Patent number
US08058476B2

Reaction notes

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