Ammonia → Donepezil Hydrochloride

HRID 456985

Reaction equation

HRID 456985 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]2[CH2:9][CH:10]([CH2:13][CH:14]3[CH2:19][CH2:18][N:17]([CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH2:16][CH2:15]3)[C:11](=[O:12])[C:6]2=[CH:5][C:4]=1[O:27][CH3:28].C(O)(C(O)=O)=O.[Cl:35]CCl.N>O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]2[CH2:9][CH:10]([CH2:13][CH:14]3[CH2:15][CH2:16][N:17]([CH2:20][C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH2:18][CH2:19]3)[C:11](=[O:12])[C:6]2=[CH:5][C:4]=1[O:27][CH3:28].[ClH:35]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 6344DichloromethaneHCID 11397232Donepezil Oxalate

Product 1

HCID 5741Donepezil Hydrochloride

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

Donepezil oxalate (purified, example 2), 5 gms, was dissolved in water 50 ml under heating at 50° C. Stirring was continued for 1 hour with gradual cooling. At room temperature, dichloromethane 50 ml was added and stirred for 10 mins. Liquid Ammonia 5 ml was added slowly with stirring. The dichloromethane layer was separated and 50 ml water was added to it. Analytical grade concentrated hydrochloric acid 1.5 ml was slowly added and stirred for 10 mins. Dichloromethane was distilled off under vacuum at 45° C. to obtain Donepezil hydrochloride in water, which was kept for lyophilyzation for 24 hours at −35° C. to give Donepezil hydrochloride amorphous with a yield of 3.9 gms (95%).

Workup

  1. stirringstirred for 10 mins
  2. stirringwith stirring
  3. customThe dichloromethane layer was separated
  4. addition50 ml water was added to it
  5. additionAnalytical grade concentrated hydrochloric acid 1.5 ml was slowly added
  6. stirringstirred for 10 mins
  7. distillationDichloromethane was distilled off under vacuum at 45° C.

Sources & evidence

ORD record
ord-e33fa25e0ded41f99fecc6aa58b18729
Source dataset
uspto-grants-2007_03
Patent number
US07186842B2

Linked notes

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