Acetic Acid → Fexofenadine

HRID 582811Notes

Reaction equation

HRID 582811 reaction equation
[OH:1][CH:2]([C:26]1[CH:31]=[CH:30][C:29]([C:32]([CH3:39])([CH3:38])[C:33]([O:35]CC)=[O:34])=[CH:28][CH:27]=1)[CH2:3][CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([C:12]([OH:25])([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:8][CH2:7]1.[OH-].[Na+].C(O)(=O)C>CO>[OH:25][C:12]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[CH:9]1[CH2:10][CH2:11][N:6]([CH2:5][CH2:4][CH2:3][CH:2]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([CH3:39])([CH3:38])[C:33]([OH:35])=[O:34])=[CH:28][CH:27]=2)[OH:1])[CH2:7][CH2:8]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 9849889Ethyl Fexofenadine

Product 1

HCID 3348FexofenadineYield 89%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
22 °C

Procedure

Ethyl 4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-α,α-dimethylbenzeneacetate (0.5 g) was dissolved in MeOH (10 mL), and sodium hydroxide solution (0.35 g, water 3 mL) was added. The reaction mixture was heated at reflux for 5 h, and cooled to 22° C., followed by the addition of acetic acid to reach a pH 4-5. MeOH (5 mL) was added to the solution and stirred for 1 h. The precipitate was collected by filtration to give 0.42 g of 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid. 1H NMR (DMSO-d6) d 1.45-1.49 (m, 2H), 1.67 (s, 6H), 1.67-1.78 (m, 6H), 2.12-2.20 (m, 2H), 2.45-2.50 (m, 2H), 2.68-2.78 (m 3H), 3.10 (broad s, 2H), 4.71 (m, 1H), 5.50 (broad s, 1H), 7.35-7.40 (m, 2H), 7.45-7.55 (m, 8H), 7.76-7.78 (m, 4H). MH+ 502.3

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 5 h
  3. filtrationThe precipitate was collected by filtration

Sources & evidence

ORD record
ord-b94f88f8247347e1b0626b4adf05dcec
Source dataset
uspto-grants-1999_07
Patent number
US05925761

Reaction notes

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