1,1-Dichloroethane → 4-(4-Methoxyphenyl)piperidine

HRID 368836Notes

Reaction equation

HRID 368836 reaction equation
C([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)C1C=CC=CC=1.ClC(Cl)C.ClC(OC(Cl)=O)C>>[CH3:21][O:20][C:17]1[CH:16]=[CH:15][C:14]([CH:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)=[CH:19][CH:18]=1

Participants

4

Reactant 3

HCID 63651,1-DichloroethaneHCID 5213051-Chloroethyl chloroformateHCID 232889401-Benzyl-4-(4-methoxyphenyl)piperidine

Product 1

HCID 106792704-(4-Methoxyphenyl)piperidine

Procedure

A mixture of 1-benzyl-4-(4-methoxy)phenylpiperidine (XVIII, Step 3, 0.4724 g, 1.7 mmol), dichloroethane (4.4 ml) and 1-chloroethylchloroformate (0.66 ml, 6.1 mmol) is refluxed overnight, then concentrated and the residue refluxed in methanol for 2 hours. After cooling, the solvent is removed and the resulting solids are slurried in dichloromethane. Ether is added and the solids are collected and then partitioned between dichloromethane and saturated sodium bicarbonate. The combined organic phases are backwashed with saline, dried over magnesium sulfate, and concentrated to give a residue which is chromatographed on silica gel eluting with methanol/dichloromethane (4/96) containing ammonium hydroxide (0.4%), followed by methanol/dichloromethane (6/94) containing ammonium hydroxide (0.4%). The appropriate fractions are pooled and concentrated to give 4-(4-methoxyphenyl)piperidine (XIX), NMR (CDCl3) 1.66, 1.83, 2.06, 2.58, 2.76, 3.21, 3.79. 6.85 and 7.15 δ.

Workup

  1. temperatureis refluxed overnight
  2. concentrationconcentrated
  3. temperaturethe residue refluxed in methanol for 2 hours
  4. temperatureAfter cooling
  5. customthe solvent is removed
  6. additionEther is added
  7. customthe solids are collected
  8. custompartitioned between dichloromethane and saturated sodium bicarbonate
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated
  11. customto give a residue which
  12. customis chromatographed on silica gel eluting with methanol/dichloromethane (4/96)
  13. additioncontaining ammonium hydroxide (0.4%)
  14. additioncontaining ammonium hydroxide (0.4%)
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-e2b8e5ee59f54c9ba3132829347a0065
Source dataset
uspto-grants-2000_10
Patent number
US06133446

Reaction notes

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