Hydrochloric Acid → 1-Benzyl-3-(3-methoxyphenyl)piperidin-3-ol

HRID 1712021Notes

Reaction equation

HRID 1712021 reaction equation
[Mg].Br[C:3]1[CH:4]=[C:5]([O:9][CH3:10])[CH:6]=[CH:7][CH:8]=1.[CH2:11]([N:18]1[CH2:23][CH2:22][CH2:21][CH2:20][C:19]1=O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Cl.C1C[O:29]CC1>>[CH2:11]([N:18]1[CH2:23][CH2:22][CH2:21][C:20]([C:3]2[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[CH:4]=2)([OH:29])[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran3×HCID 169713-BromoanisoleHCID 51700761-Benzyl-2-piperidoneHCID 5462224Magnesium

Product 1

HCID 136950931-Benzyl-3-(3-methoxyphenyl)piperidin-3-ol

Conditions

Temperature
50 °C

Procedure

4.22 g magnesium (Mg) in 50 mL THF and a speck of 12 were placed under a nitrogen atmosphere in a three-necked flask equipped with condenser, internal thermometer and dropping funnel. The mixture was heated to 50° C. while stirring and 22.1 ml of 3-bromoanisole in 50 ml THF were added dropwise within 30 minutes. The mixture was then stirred for a further 30 minutes at 70° C. After cooling with ice to 5° C., 22.34 g of N-benzyl-piperidone in 100 ml THF were added dropwise in 60 minutes. The mixture was stirred for a further 15 hours at room temperature. For the hydrolysis, 400 ml of 10% NH4HSO4 solution were added, acidified with dilute HCl, and then extracted with 100 ml of diethyl ether. The organic phase was extracted once with dilute HCl. The combined aqueous phases were made alkaline with NaOH and extracted three times with 100 ml portions of diethyl ether each time. The combined organic phases were concentrated by evaporation. Yield 35.05 g

Workup

  1. customequipped with condenser
  2. stirringThe mixture was then stirred for a further 30 minutes at 70° C
  3. temperatureAfter cooling with ice to 5° C.
  4. stirringThe mixture was stirred for a further 15 hours at room temperature
  5. additionwere added
  6. extractionextracted with 100 ml of diethyl ether
  7. extractionThe organic phase was extracted once with dilute HCl
  8. extractionextracted three times with 100 ml portions of diethyl ether each time
  9. concentrationThe combined organic phases were concentrated by evaporation

Sources & evidence

ORD record
ord-2698ab4665d8483295d9d7bdbe5e7949
Source dataset
uspto-grants-2010_09
Patent number
US07790898B2

Reaction notes

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