Phenol → HCID 22729919, compound

HRID 2085454Notes

Reaction equation

HRID 2085454 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=2)(O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23]1([OH:29])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[Al+3].[Cl-].[Cl-].[Cl-]>[NH4+].[OH-]>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:26]2[CH:27]=[CH:28][C:23]([OH:29])=[CH:24][CH:25]=2)([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 6451240Aluminum(III) ChlorideHCID 22397834HCID 22397834, compound

Product 1

HCID 22729919HCID 22729919, compoundYield 73.6%

Reagents, catalysts & solvents 1

HCID 14923Ammonium HydroxideSolvent

Procedure

To a solution of 1-Benzyl-4-(3-methoxy-phenyl)-piperidin-4-ol (21.7 g, 73.1 mmol) in (CH2)2Cl2 (200 mL) was added phenol (20.7 g, 220 mmol) followed by portionwise addition (highly exothermic) of AlCl3 (29.3 g, 200 mmol). The reaction mixture was heated to reflux for 10 hours. The mixture was cooled to room temperature and was slowly poured into a mixture of crushed ice (50 mL) and 30% aq. NH4OH (120 mL). The mixture was stirred vigorously for 20 minutes and was then filtered through celite. The celite cake was washed with CH2Cl2 (200 mL). The organic layer was separated and the aqueous layer was washed with CH2Cl2 (3×100 mL). The combined organic layers were dried (MgSO4) and concentrated. The crude residue was purified by flash chromatography with hexanes/EtOAc (1:1) to afford 20.1 g (73% yield) of 4-[1-Benzyl-4-(3-methoxy-phenyl)-piperidin-4-yl]-phenol. 1HNMR (400 MHz, CD3OD) δ 7.28-7.20 (comp, 5H), 7.14 (t, 1H), 7.07 (d, 2H), 6.83 (d, 2H), 6.76 (s, 1H), 6.70-6.60 (comp, 3H), 3.69 (s, 3H), 3.39 (s, 2H), 2.50-2.40 (comp, 4H), 2.39-2.29 (comp, 4H); MS (M+1) 374.2.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 10 hours
  3. filtrationwas then filtered through celite
  4. washThe celite cake was washed with CH2Cl2 (200 mL)
  5. customThe organic layer was separated
  6. washthe aqueous layer was washed with CH2Cl2 (3×100 mL)
  7. dry with materialThe combined organic layers were dried (MgSO4)
  8. concentrationconcentrated
  9. customThe crude residue was purified by flash chromatography with hexanes/EtOAc (1:1)

Sources & evidence

ORD record
ord-799761086fa3465685120b399f09ff6c
Source dataset
uspto-grants-2004_04
Patent number
US06720336B2

Reaction notes

Loading…