Hydrochloric Acid → 1-(4-Hydroxy-4-[4-methoxyphenyl]piperidin-1-yl)ethanone

HRID 1940538Notes

Reaction equation

HRID 1940538 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.[Mg].[C:11]([N:14]1[CH2:19][CH2:18][C:17](=[O:20])[CH2:16][CH2:15]1)(=[O:13])[CH3:12].Cl>O1CCCC1>[OH:20][C:17]1([C:2]2[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=2)[CH2:18][CH2:19][N:14]([C:11](=[O:13])[CH3:12])[CH2:15][CH2:16]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 77304-BromoanisoleHCID 122563N-Acetyl-4-piperidoneHCID 5462224Magnesium

Product 1

HCID 214629681-(4-Hydroxy-4-[4-methoxyphenyl]piperidin-1-yl)ethanoneYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

4-Bromoanisole (22.4 g, 0.12 mol) in tetrahydrofuran (180 ml) was slowly added to magnesium (2.9 g, 0.12 mol) in tetrahydrofuran (20 ml) and the mixture stirred for one hour at room temperature. The solution formed was slowly added to a solution of 1-acetyl-4-piperidone (16.9 g, 0.12 mol) in tetrahydrofuran (200 ml) at -78° C., and the suspension produced was stirred to room temperature for 2 hours. Hydrochloric acid (120 ml, 1M) was added and the organic phase was separated and concentrated in vacuo. The residue was taken up in dichloromethane (300 ml), washed with water (300 ml) and dried (MgSO4). Concentration in vacuo and trituration with diethyl ether gave 1-[4-hydroxy-4-(4-methoxyphenyl)-piperidin-1-yl]ethanone (14.75 g, 50% yield) as a white solid; δH (CDCl3) 1.7-2.1 (4H, m, 2× piperidinyl CH2), 2.1 (3H, s, COCH3), 3.1 (1H, m, piperidinyl H), 3.6-3.8 (3H, m, piperidinyl H), 3.8 (3H, s, ArOCH3), 4.6 (1H, m, OH), 6.9 (2H, d, J 10 Hz, ArH), and 7.4 (2H, d, J 10 Hz, ArH).

Workup

  1. customThe solution formed
  2. customthe suspension produced
  3. stirringwas stirred to room temperature for 2 hours
  4. customthe organic phase was separated
  5. concentrationconcentrated in vacuo
  6. washwashed with water (300 ml)
  7. dry with materialdried (MgSO4)
  8. concentrationConcentration in vacuo and trituration with diethyl ether

Sources & evidence

ORD record
ord-9cccd0bdddef4f139894a4eb2d115c3c
Source dataset
uspto-grants-1997_12
Patent number
US05700809

Reaction notes

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