Water → Fexofenadine Hydrochloride

HRID 1445533Notes

Reaction equation

HRID 1445533 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>C(C(C)=O)C>[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 962Water3×HCID 116137484-[(4-(Hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha,alpha-dimethylbenzeneacetic acid hydrochloride hydrate2×

Product 1

HCID 63002Fexofenadine HydrochlorideYield 182.4%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent2×

Conditions

Temperature
-15 °C

Procedure

Treat 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride hydrate (Form II) (40.0 g, 0.0696 mol, assayed at 93.6% purity, having 0.89 g water present and 35.1 g, 0.0575 mol, assayed at 88.0% purity, having 2.47 g water present) with water (8.30 g; the amount calculated to bring the weight of water present to 17% of the anhydrous weight of 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride hydrate, taking into account the water in the hydrated salt). Add methyl ethyl ketone (approximately 500 mL) and stir until most of the solids dissolve. Add additional methyl ethyl ketone (700 mL) in portions over approximately 10 minutes and continue stirring for ½ hour. Filter through a thin pad of filter aid, wash the filtercake and flask with additional methyl ethyl ketone (100 mL) and transfer to a boiling flask fitted with a thermometer, mechanical stirrer, heating mantle, a 12-plate Oldershaw (vacuum-jacketed) distillation column and a distillation head with the capability of regulating the reflux ratio in a rough fashion, washing in with additional methyl ethyl ketone (100 mL). Distill off 450 mL of solvent, cool to −15° C. and filter the solid. Wash with methyl ethyl ketone (2×100 mL) and dry to give the title compound (68.3 g, 99.9%); mp 197-199° C.

Workup

  1. dissolutiondissolve
  2. filtrationFilter through a thin pad of filter aid
  3. washwash the filtercake and flask with additional methyl ethyl ketone (100 mL)
  4. customtransfer to a boiling flask
  5. customfitted with a thermometer, mechanical stirrer
  6. temperatureheating mantle
  7. distillationa 12-plate Oldershaw (vacuum-jacketed) distillation column
  8. washwashing in with additional methyl ethyl ketone (100 mL)
  9. distillationDistill off 450 mL of solvent
  10. filtrationfilter the solid
  11. washWash with methyl ethyl ketone (2×100 mL)
  12. customdry

Sources & evidence

ORD record
ord-0844de2d78914db58b5ea745a6a8c3b4
Source dataset
uspto-grants-2010_02
Patent number
US07666881B2

Reaction notes

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