Hydrochloric Acid → Donepezil Hydrochloride

HRID 1454362Notes

Reaction equation

HRID 1454362 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(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

4

Reactant 2

HCID 313Hydrochloric AcidHCID 3152Donepezil

Product 1

HCID 5741Donepezil HydrochlorideYield 96.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
9 °C

Procedure

50 g of donepezil was dissolved by stirring in 280 g of ethanol under heating, followed by adding 15.1 g of concentrated hydrochloric acid thereto at the internal temperature of 28° C. Then, it was cooled and continued stirring while keeping the internal temperature at about 25° C. Crystals started precipitating about 40 minutes after the concentrated hydrochloric acid was poured into the mixture. After the precipitation started, the mixture was stirred at the internal temperature of 25° C. for 18 hours and then cooled to the internal temperature of 9° C. The crystals were collected by filtration and dried about 4 hours after the cooling was started, to give 52.81 g of polymorphic crystal (III) of donepezil hydrochloride (yield: 96.4%).

Workup

  1. temperatureunder heating
  2. customat the internal temperature of 28° C
  3. temperatureThen, it was cooled
  4. customat about 25° C
  5. customCrystals started precipitating about 40 minutes after the concentrated hydrochloric acid
  6. additionwas poured into the mixture
  7. customAfter the precipitation
  8. stirringthe mixture was stirred at the internal temperature of 25° C. for 18 hours
  9. filtrationThe crystals were collected by filtration
  10. customdried about 4 hours after the cooling

Sources & evidence

ORD record
ord-fcf6b4a72e9c473bbc2c71da1d9711d1
Source dataset
uspto-grants-2009_01
Patent number
US07479563B2

Reaction notes

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