Ammonia → N,N-Didesmethylvenlafaxine

HRID 349735Notes

Reaction equation

HRID 349735 reaction equation
CO.N.[C:4]([CH:6]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:7]1([OH:13])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)#[N:5]>[Ni].C(O)(=O)C>[NH2:5][CH2:4][CH:6]([C:7]1([OH:13])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)[C:14]1[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=1

Participants

6

Reactant 3

HCID 222AmmoniaHCID 887Methanol2×HCID 9899621(1-Hydroxycyclohexyl)(4-methoxyphenyl)acetonitrile

Product 1

HCID 9795857N,N-DidesmethylvenlafaxineYield 70%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 176Acetic AcidSolvent2×

Procedure

The reactor was charged with 25.0 g of Raney-Ni (Kawaken, Grace 2400, 2724, Degussa B111W, 112W), and 250 ml of MeOH and 25 ml of an ammonia solution (25% NH3) were added. To the mixture was added 50 g of 1-[cyano(4-methoxyphenyl)methyl]cyclohexanol, followed by 250 ml of MeOH. The reactor was settled and purged with N2 gas two or three times. After fully purged with N2, the reactor was purged with H2 gas two or three times. Internal pressure of the reactor was adjusted to 60 psi and the reaction mixture was stirred. After 20 to 30 hours of reaction at room temperature (about 10 to 20° C.), in-process analysis of a sample of mixture was made. After the reaction was completed, Ra—Ni was removed by filtration with a celite pad. The filtrate was distilled under reduced pressure until all of the solvent was evaporated, and 200 ml of isopropyl alcohol and 400 ml of ethyl acetate were added to the residue oil to dissolve the resulting product to give a clear or a little hazy solution. To the solution was added 10 ml of acetic acid dropwise, and an exothermic reaction began with some fumes given off. After about 10 to 20 minutes of adding all of the acetic acid, a solid began to form. The solution was stirred for about one hour, filtered and washed with ethyl acetate to give the desired product, 1-[2-amino-1-(4-methoxyphenyl)ethyl]-cyclohexanol, 44.2 g (yield 70%, purity 99%).

Workup

  1. additionwere added
  2. custompurged with N2 gas two or three times
  3. customAfter fully purged with N2
  4. customthe reactor was purged with H2 gas two or three times
  5. customAfter 20 to 30 hours of reaction at room temperature (about 10 to 20° C.)
  6. customRa—Ni was removed by filtration with a celite pad
  7. distillationThe filtrate was distilled under reduced pressure until all of the solvent
  8. customwas evaporated
  9. addition200 ml of isopropyl alcohol and 400 ml of ethyl acetate were added to the residue oil
  10. dissolutionto dissolve the resulting product
  11. customto give a clear or a little hazy solution
  12. customan exothermic reaction
  13. customto form
  14. stirringThe solution was stirred for about one hour
  15. filtrationfiltered
  16. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-3fda28f6fd95419abd5b11a2bcd39d64
Source dataset
uspto-grants-2007_02
Patent number
US07179944B2

Reaction notes

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