Ammonia → N,N-Didesmethylvenlafaxine hydrochloride

HRID 724501Notes

Reaction equation

HRID 724501 reaction equation
[C:1]([CH:3]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1)[C:4]1([OH:10])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1)#[N:2].N.[H][H].[ClH:22]>[Ni].C(OCC)(=O)C.CO>[ClH:22].[NH2:2][CH2:1][CH:3]([C:4]1([OH:10])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1)[C:11]1[CH:12]=[CH:13][C:14]([O:17][CH3:18])=[CH:15][CH:16]=1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 9899621(1-Hydroxycyclohexyl)(4-methoxyphenyl)acetonitrileHCID 178418361HCID 178418361, compound

Product 1

HCID 9795856N,N-Didesmethylvenlafaxine hydrochloride

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 5 liter autoclave is charged with 180 g of 1-[cyano(4-methoxyphenyl)methyl]cyclohexanol, 2400 ml of methanol, 600 ml of aqueous ammonia (25% by volume) and 135 g of Raney nickel (pretreated as given under 1a)) and the mixture is subjected to hydrogenation at 27 to 30° C. and 120 psi pressure of hydrogen for 9 to 10 hours. The reaction mixture is filtered through 100 g of the celite and the catalyst bed is washed with 700 ml of methanol. The filtrate is concentrated to get 167.1 g of the crude product as an oily residue. 1.1 g of the crude product is dissolved in 2 ml of dry ethyl acetate and about 2 ml of isopropanolic HCl are added (the pH of the solution is about 2). The solvent is removed at high vacuum to give 1.14 g of 1-[2-amino-1-(4-methoxyphenyl)ethyl]cyclohexanol hydrochloride.

Workup

  1. customis subjected to hydrogenation at 27 to 30° C.
  2. filtrationThe reaction mixture is filtered through 100 g of the celite
  3. washthe catalyst bed is washed with 700 ml of methanol
  4. concentrationThe filtrate is concentrated
  5. customto get 167.1 g of the crude product as an oily residue
  6. customThe solvent is removed at high vacuum

Sources & evidence

ORD record
ord-99255fbce637460caa27a88dc49892b4
Source dataset
uspto-grants-2006_11
Patent number
US07141697B2

Reaction notes

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