Acetone → 1-[2-(2-Tert-butyl-5-nitro-phenoxy)-ethyl]-piperidine

HRID 2109581Notes

Reaction equation

HRID 2109581 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:6]=1[OH:14])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].CC(C)=O.Cl.Cl[CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1>CCCC[N+](CCCC)(CCCC)CCCC.[I-].O>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:6]=1[O:14][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 180AcetoneHCID 11430Potassium Carbonate2×HCID 74826Piperidine, 1-(2-chloroethyl)-, hydrochloride2×HCID 219596172-Tert-butyl-5-nitrophenol

Product 1

HCID 219595061-[2-(2-Tert-butyl-5-nitro-phenoxy)-ethyl]-piperidine

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 962WaterSolvent

Procedure

To 2-tert-butyl-5-nitrophenol (1.01 g) and K2CO3 (1.72 g) was added acetone (35 ml) and H2O (10.5 mL), then 1-(2-chloroethyl)piperidine HCl (1.909 g) and TBAI (153 mg). The mixture was stirred at reflux overnight. Additional K2CO3 (850 mg) and 1-(2-chloroethyl)-piperidine HCl (950 mg) were added and the mixture was heated at reflux for 6 h. The mixture was concentrated in vacuo to an aqueous layer which was acidified with 2 N HCl and extracted with EtOAc. The aqueous layer was basified with 6 N NaOH and washed with CH2Cl2 (3×). The combined organic layers were washed with brine/1 N NaOH and dried over Na2SO4. Washed the EtOAc layer with 2 N NaOH/brine and dried over Na2SO4. The crude material was purified by silica gel column chromatography with 15% EtOAc/Hexanes to yield 1-[2-(2-tert-butyl-5-nitro-phenoxy)-ethyl]-piperidine as a light tan solid. (M+1)=307.3.

Workup

  1. temperatureat reflux overnight
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 6 h
  4. concentrationThe mixture was concentrated in vacuo to an aqueous layer which
  5. extractionextracted with EtOAc
  6. washwashed with CH2Cl2 (3×)
  7. washThe combined organic layers were washed with brine/1 N NaOH
  8. dry with materialdried over Na2SO4
  9. washWashed the EtOAc layer with 2 N NaOH/brine
  10. dry with materialdried over Na2SO4
  11. customThe crude material was purified by silica gel column chromatography with 15% EtOAc/Hexanes

Sources & evidence

ORD record
ord-653b8fe1a39842239215a791c5d70cb3
Source dataset
uspto-grants-2009_04
Patent number
US07514564B2

Reaction notes

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