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

HRID 557317Notes

Reaction equation

HRID 557317 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 2N HCl and extracted with EtOAc. The aqueous layer was basified with 6N NaOH and washed with CH2Cl2 (3×). The combined organic layers were washed with brine/1N NaOH and dried over Na2SO4. Washed the EtOAc layer with 2N 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/1N NaOH
  8. dry with materialdried over Na2SO4
  9. washWashed the EtOAc layer with 2N 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-b37610b00d6d4fcfbfbe44f94aed7932
Source dataset
uspto-grants-2011_11
Patent number
US08058445B2

Reaction notes

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