Sodium Hydroxide → Fexofenadine

HRID 644790Notes

Reaction equation

HRID 644790 reaction equation
Cl.[OH:2][C:3]([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:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][C:13]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([CH3:27])([CH3:26])[C:22]([O:24]C)=[O:23])=[CH:17][CH:16]=2)=[O:14])[CH2:6][CH2:5]1.Cl.OC(C1C=CC=CC=1)(C1C=CC=CC=1)C1CCN(CCCC(C2C=C(C(C)(C)C(OC)=O)C=CC=2)=O)CC1.[OH-].[Na+].[BH4-].[Na+]>CO.C(O)(=O)C.CC(C)=O.O>[CH3:27][C:21]([C:22]([OH:24])=[O:23])([C:18]1[CH:19]=[CH:20][C:15]([CH:13]([OH:14])[CH2:12][CH2:11][CH2:10][N:7]2[CH2:6][CH2:5][CH:4]([C:3]([OH:2])([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:9][CH2:8]2)=[CH:16][CH:17]=1)[CH3:26]

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 22471930Methyl 2-(4-(4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butanoyl)phenyl)-2-methylpropanoate hydrochlorideHCID 68469874Methyl 3-[4-[4-(hydroxydiphenylmethyl)1-piperidinyl]-1-oxobutyl]-alpha,alpha-dimethylbenzeneacetate hydrochloride

Product 1

HCID 3348Fexofenadine

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 180AcetoneSolventHCID 887MethanolSolvent2×HCID 962WaterSolvent

Procedure

To a solution of a mixture of methyl 4-[4-[4-(hydroxydiphenylmethyl)1-piperidinyl]-1-oxobutyl]-α,α-dimethylbenzeneacetate hydrochloride and methyl 3-[4-[4-(hydroxydiphenylmethyl)1-piperidinyl]-1-oxobutyl]-α,α-dimethylbenzeneacetate hydrochloride (100 g) in methanol (600 ml) is added aqueous sodium hydroxide (36.4 g sodium hydroxide in 132 ml of water). The mixture is heated to reflux for about 2-4 hours. Completion of the reaction is monitored by TLC method and upon completion the reaction mixture is cooled to ambient temperature accompanied by addition of sodium borohydride (6.8 g). The reaction mixture is heated to 50-60° C. and maintained at the same temperature for about 14 hours (completion of the reaction is monitored by TLC method), and subsequently cooled to ambient temperature accompanied by carbon treatment. The clear filtrate obtained after carbon treatment, is stripped of methanol followed by addition of water (300 ml) and acetone (200 ml). The pH of the reaction mixture is then adjusted to ˜6 with acetic acid, stirred for 5 hours and then filtered, followed by water wash (200 ml) to afford crude Fexofenadine.

Workup

  1. temperatureThe mixture is heated
  2. temperatureto reflux for about 2-4 hours
  3. temperatureThe reaction mixture is heated to 50-60° C.
  4. temperaturemaintained at the same temperature for about 14 hours (completion of the reaction
  5. temperaturesubsequently cooled to ambient temperature
  6. customThe clear filtrate obtained after carbon treatment
  7. filtrationfiltered
  8. washwash (200 ml)

Sources & evidence

ORD record
ord-bebe0b46b91b4623b19b54b694fef35a
Source dataset
uspto-grants-2010_04
Patent number
US07700779B2

Reaction notes

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