Hydrochloric Acid → Donepezil Hydrochloride

HRID 1714126Notes

Reaction equation

HRID 1714126 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[CH2:14][CH:13]([CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([CH2:22][C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH2:18][CH2:17]3)[C:11](=[O:12])[C:6]2=[CH:7][C:8]=1[O:9][CH3:10].[ClH:29].C(OC(C)C)(C)C>C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[CH2:14][CH:13]([CH2:15][CH:16]3[CH2:17][CH2:18][N:19]([CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH2:20][CH2:21]3)[C:11](=[O:12])[C:6]2=[CH:7][C:8]=1[O:9][CH3:10].[ClH:29]

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 3152DonepezilHCID 7914Diisopropyl Ether

Product 1

HCID 5741Donepezil HydrochlorideYield 96.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

After completing the hydrogenation, the catalyst was removed from the reaction solution followed by concentration. To the concentrated residue, 91 ml of ethanol was added to obtain a solution. Subsequently, the solution was crystallized under stirring. Precipitated crystals were filtered out, and then dried to obtain 10.6 g of donepezil. The obtained donepezil (9 g) was dissolved in 80 ml of ethanol. A mixed liquid of 2.7 g of concentrated hydrochloric acid and 10 ml of ethanol was added to the reaction solution under stirring, and the mixture was converted into its hydrochloride. After adding 135 ml of diisopropyl ether, the precipitated crystals were filtered out, and then dried to obtain 9.5 g of donepezil hydrochloride. The values of 1H-NMR of donepezil hydrochloride were consistent with those of Example 3.

Workup

  1. filtrationthe precipitated crystals were filtered out
  2. customdried

Sources & evidence

ORD record
ord-c7a2ed582dfb411ba159c2056babc4a8
Source dataset
uspto-grants-2010_09
Patent number
US07795438B2

Reaction notes

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