Water → Fexofenadine Hydrochloride

HRID 1445532Notes

Reaction equation

HRID 1445532 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 962WaterHCID 116137484-[(4-(Hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha,alpha-dimethylbenzeneacetic acid hydrochloride hydrate

Product 1

HCID 63002Fexofenadine HydrochlorideYield 98%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent2×

Conditions

Temperature
-15 °C

Procedure

Mix 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride hydrate (Form II) (53.88 g, 0.100 mol) and add water (4.79 g) and methyl ethyl ketone (240 mL). Stir until the solid is slurried up and add additional methyl ethyl ketone (1 L). Stir for 0.5 hours, filter through a pad of filter aid, wash the filtercake with methyl ethyl ketone (100 mL) and transfer the filtrate and wash to a 2 L, 3-necked flask fitted with a thermometer, mechanical stirrer and distillation head. Distill off a total of 721 mL of methyl ethyl ketone, cool and stir over 1 hour to 40° C. Cool to −15° C. and hold for 10 minutes. Collect the solid by vacuum filtration and wash the filtercake with methyl ethyl ketone (2×65 mL) and vacuum dry at 55° C. overnight to give the title compound (52.76 g, 97.9%); mp 197.5-200° C.

Workup

  1. stirringStir for 0.5 hours
  2. filtrationfilter through a pad of filter aid
  3. washwash the filtercake with methyl ethyl ketone (100 mL)
  4. washwash to a 2 L, 3-necked flask
  5. customfitted with a thermometer, mechanical stirrer and distillation head
  6. distillationDistill off a total of 721 mL of methyl ethyl ketone
  7. temperaturecool
  8. stirringstir over 1 hour to 40° C
  9. customCollect the solid
  10. filtrationby vacuum filtration
  11. washwash the filtercake with methyl ethyl ketone (2×65 mL) and vacuum
  12. customdry at 55° C. overnight

Sources & evidence

ORD record
ord-45a849bfecd14a3fa0fa71c5b4015b53
Source dataset
uspto-grants-2010_02
Patent number
US07666881B2

Reaction notes

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