2-Chlorophenol → 1-Benzyl-4-(4-methoxybenzylidene)-piperidine

HRID 1783323Notes

Reaction equation

HRID 1783323 reaction equation
C(OC(N1CC[CH:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2Cl)CC1)=O)(C)(C)C.C(O[C:27]([N:29]1[CH2:34][CH2:33][CH:32](O)[CH2:31][CH2:30]1)=O)(C)(C)C.Cl[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1O.[C:44]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>CCOC(C)=O>[CH2:27]([N:29]1[CH2:30][CH2:31][C:32](=[CH:44][C:18]2[CH:17]=[CH:16][C:15]([O:14][CH3:11])=[CH:20][CH:19]=2)[CH2:33][CH2:34]1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

7

Reactant 5

HCID 72452-ChlorophenolHCID 11776TriphenylphosphineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 5363146Diisopropyl azodicarboxylateHCID 16732586Tert-butyl 4-(2-chlorophenoxy)piperidine-1-carboxylate

Product 1

HCID 223788701-Benzyl-4-(4-methoxybenzylidene)-piperidine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

4-(2-Chlorophenoxy)-piperidine-1-carboxylic acid tert-butyl ester (10.6) This compound was prepared from 4-hydroxypiperidine-1-carboxylic acid tert-butyl ester (9) (3.505 g; 17.4 mmol), 2-chloro-phenol (3.375 g; 26.3 mmol), triphenylphosphine (6.002 g; 22.9 mmol) and DIAD (4.30 mL; 21.8 mmol) in a manner analogous to 10.5. After 8 days, EtOAc (200 mL) was added to the crude reaction mixture and the solution washed with 50% saturated NaHCO3 (50 mL), saturated NaHCO3 (2×25 mL) and saturated NaCl (2×25 mL) then dried (MgSO4), filtered and concentrated to a viscous liquid. Ether (50 mL) and hexanes (50 mL) were added and this was allowed to stand overnight; whereupon the precipitate was removed by filtration and the filtrate partially concentrated. More material precipitated, which was also removed by filtration, and the filtrate was concentrated to an oil. The product was partially purified on basic alumina (160 mL), eluting with 8:1 hexanes:EtOAc, giving a clear, colorless viscous liquid (5.12 g; 94% crude yield). LC (method A) tR=11.50 min; ESIMS 312.1/314.1 (1/0.3) [MH+], 296.9/298.9 (100/34) [MH+−C4H9+CH3CN], 255.9/257.8 (41/12) [MH+−C4H9], 212.0/214.0 (4/1)[MH+−C4H9−CO2].

Workup

  1. customreaction mixture
  2. washthe solution washed with 50% saturated NaHCO3 (50 mL), saturated NaHCO3 (2×25 mL) and saturated NaCl (2×25 mL)
  3. dry with materialthen dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated to a viscous liquid
  6. additionEther (50 mL) and hexanes (50 mL) were added
  7. waitto stand overnight
  8. customwhereupon the precipitate was removed by filtration
  9. concentrationthe filtrate partially concentrated
  10. customMore material precipitated
  11. customwhich was also removed by filtration
  12. concentrationthe filtrate was concentrated to an oil
  13. customThe product was partially purified on basic alumina (160 mL)
  14. washeluting with 8:1 hexanes
  15. customEtOAc, giving a clear, colorless viscous liquid (5.12 g; 94% crude yield)

Sources & evidence

ORD record
ord-8c82bb2c21d64f9d9787abb9f1b3766d
Source dataset
uspto-grants-2009_03
Patent number
US07501407B2

Reaction notes

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