Sodium Hydroxide → Hydroxyterfenadine

HRID 895076Notes

Reaction equation

HRID 895076 reaction equation
[OH:1][C:2]([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:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][CH2:11][CH:12]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([CH3:27])([CH3:26])[C:21](OCC)=[O:22])=[CH:16][CH:15]=2)[OH:13])[CH2:5][CH2:4]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+].S([O-])([O-])(=O)=O.[Na+].[Na+]>O1CCCC1.O>[C:28]1([C:2]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)([CH:3]2[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][CH2:11][CH:12]([C:14]3[CH:15]=[CH:16][C:17]([C:20]([CH3:27])([CH3:26])[CH2:21][OH:22])=[CH:18][CH:19]=3)[OH:13])[CH2:5][CH2:4]2)[OH:1])[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24436Sodium SulfateHCID 9849889Ethyl FexofenadineHCID 21226445Aluminium lithium hydride

Product 1

HCID 9805485Hydroxyterfenadine

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent3×

Procedure

A suspension of 2.15 g (0.0038 mole) of ethyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetate in 50 ml of tetrahydrofuran was slowly added to a suspension of 0.7 g (0.0184 mole) of lithium aluminum hydride in 60 ml of tetrahydrofuran under a nitrogen atmosphere with stirring at such a rate to moderate the foaming. The mixture is stirred and heated at boiling for about 3 hours after which 30 ml of tetrahydrofuran is added. The mixture is refluxed for 4 hours and let stand overnight (about 16 hours). Stirring the mixture under a nitrogen atmosphere, 2 ml of water is added cautiously followed by 2 ml of 10% sodium hydroxide, 2 ml of water and 4 g of sodium sulfate. The mixture is warmed to 50°-55° C. and stirred for 45 minutes, filtered and the solid material is washed with tetrahydrofuran. The combined filtrates are evaporated in vacuo, and the residue is recrystallized from ethanol to give α,α-diphenyl-1-[4-[4-hydroxy-tert-butyl)phenyl]-4-hydroxybutyl]-4-piperidinemthanol, M.P. 134°-136° C.

Workup

  1. stirringThe mixture is stirred
  2. temperatureheated
  3. temperatureThe mixture is refluxed for 4 hours
  4. waitlet stand overnight
  5. custom(about 16 hours)
  6. stirringStirring the mixture under a nitrogen atmosphere
  7. temperatureThe mixture is warmed to 50°-55° C.
  8. stirringstirred for 45 minutes
  9. filtrationfiltered
  10. washthe solid material is washed with tetrahydrofuran
  11. customThe combined filtrates are evaporated in vacuo
  12. customthe residue is recrystallized from ethanol
  13. customto give α,α-diphenyl-1-[4-[4-hydroxy-tert-butyl)phenyl]-4-hydroxybutyl]-4-piperidinemthanol, M.P. 134°-136° C.

Sources & evidence

ORD record
ord-627da2d4422740c5a8607f93300887e8
Source dataset
uspto-grants-1981_08
Patent number
US04285957

Reaction notes

Loading…