Hydrochloric Acid → Hydroxyterfenadine

HRID 1700037Notes

Reaction equation

HRID 1700037 reaction equation
[O:1]=[C:2]([C:26]1[CH:31]=[CH:30][C:29]([C:32]([CH3:36])([CH3:35])[CH2:33][OH: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.[BH4-].[Na+].Cl>CO.O>[OH:1][CH:2]([C:26]1[CH:27]=[CH:28][C:29]([C:32]([CH3:36])([CH3:35])[CH2:33][OH:34])=[CH:30][CH:31]=1)[CH2:3][CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([C:12]([OH:25])([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:8][CH2:7]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 118129062-(4-(1-Oxo-4-(4-(hydroxydiphenylmethyl)-1-piperidinyl)-butyl)-phenyl)-2-methylpropanol

Product 1

HCID 9805485HydroxyterfenadineYield 79%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

Dissolve 2-(4-(1-oxo-4-(4-(hydroxydiphenylmethyl)-1-piperidinyl)-butyl)-phenyl)-2-methylpropanol in methanol (450 mL) and stir for 15 minutes at room temperature. Add, by dropwise addition, a solution of sodium borohydride (2.25 g, 0.06 mol) in water (10 mL) over 15 minutes. Stir for another 30 minutes and cool in an ice-bath. Slowly add concentrated hydrochloric acid (4 mL) and water (8 mL) and stir for an additional 20 minutes. Evaporate the solvent in vacuo and partition the residue between methylene chloride (150 mL) and water (70 mL). Separate the organic phase and extract the aqueous phase with methylene chloride (25 mL). Wash the combined organic layers with water (2×50 mL), evaporate the solvent in vacuo and recrystallize (acetone) to give the title compound as white needles (9.53 g, 79%).

Workup

  1. additionAdd, by dropwise addition
  2. stirringStir for another 30 minutes
  3. temperaturecool in an ice-bath
  4. stirringstir for an additional 20 minutes
  5. customEvaporate the solvent in vacuo
  6. custompartition the residue between methylene chloride (150 mL) and water (70 mL)
  7. customSeparate the organic phase
  8. extractionextract the aqueous phase with methylene chloride (25 mL)
  9. washWash the combined organic layers with water (2×50 mL)
  10. customevaporate the solvent in vacuo
  11. customrecrystallize (acetone)

Sources & evidence

ORD record
ord-616477021c2d4d1c986518853da1aa07
Source dataset
uspto-grants-2002_02
Patent number
US06348597B2

Reaction notes

Loading…