Water → Fexofenadine Hydrochloride

HRID 1091968Notes

Reaction equation

HRID 1091968 reaction equation
O.[ClH:2].[OH:3][C:4]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH:5]1[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][CH2:13][CH:14]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([CH3:27])([CH3:26])[C:23]([OH:25])=[O:24])=[CH:18][CH:17]=2)[OH:15])[CH2:7][CH2:6]1.O>CC(C)=O>[ClH:2].[OH:3][C:4]([C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[CH:5]1[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][CH2:13][CH:14]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([CH3:27])([CH3:26])[C:23]([OH:25])=[O:24])=[CH:18][CH:17]=2)[OH:15])[CH2:7][CH2:6]1

Participants

4

Reactant 2

HCID 962WaterHCID 116137484-[(4-(Hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha,alpha-dimethylbenzeneacetic acid hydrochloride hydrate

Product 1

HCID 63002Fexofenadine HydrochlorideYield 95.1%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
8 °C

Procedure

Treat 4-[4-[4-(Hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride hydrate (Form II) (20.0 g, 0.0355 mol) with deionized water (2 g) and add acetone (60 mL) in small portions over several minutes with stirring. Filter through filter aid and wash the filter cake with acetone (30 mL). Wash the filtercake with acetone (22 mL), reflux filtrate and then slowly add ethyl acetate (32 mL over 15 minutes) keeping the mixture at eflux. Reflux for 10 minutes, then slowly add additional ethyl acetate (23 mL over 10 minutes) and reflux for an additional 15 minutes. Add additional ethyl acetate (60 mL over 5-10 minutes) and continue refluxing for 15 minutes. Cool to approximately 8° C. in an ice bath, filter the solid and wash with ethyl acetate (85 mL). Vacuum dry at 55° C. for 1.5 hours to give the title compound (18.16 g, 95%).

Workup

  1. filtrationFilter
  2. filtrationthrough filter aid
  3. washwash the filter cake with acetone (30 mL)
  4. washWash the filtercake with acetone (22 mL)
  5. temperaturereflux filtrate
  6. customslowly add ethyl acetate (32 mL over 15 minutes)
  7. temperatureReflux for 10 minutes
  8. temperatureslowly add additional ethyl acetate (23 mL over 10 minutes) and reflux for an additional 15 minutes
  9. additionAdd additional ethyl acetate (60 mL over 5-10 minutes)
  10. temperaturecontinue refluxing for 15 minutes
  11. filtrationfilter the solid
  12. washwash with ethyl acetate (85 mL)
  13. customVacuum dry at 55° C. for 1.5 hours

Sources & evidence

ORD record
ord-0c5acee3bf0a4c7a831218ce30b3e84b
Source dataset
uspto-grants-2012_03
Patent number
US08129408B2

Reaction notes

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