Water → Tert-butyl 4-[2-(2-tert-butylphenoxy)ethyl]piperidine-1-carboxylate

HRID 2041965Notes

Reaction equation

HRID 2041965 reaction equation
[OH:1][CH2:2][CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.[C:17]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1O)([CH3:20])([CH3:19])[CH3:18].[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>N1C=CC=CC=1.CN(C=O)C>[C:17]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[O:1][CH2:2][CH2:3][CH:4]1[CH2:5][CH2:6][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:8][CH2:9]1)([CH3:20])([CH3:19])[CH3:18]

Participants

7

Reactant 4

HCID 962WaterHCID 69232-Tert-ButylphenolHCID 62657Potassium Phosphate, TribasicHCID 8541401-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidine

Product 1

HCID 59577273Tert-butyl 4-[2-(2-tert-butylphenoxy)ethyl]piperidine-1-carboxylateYield 121.8%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

To an ice-cold stirred solution of tert-butyl 4-(2-hydroxyethyl)piperidine-1-carboxylate (44.3 g, 193 mmol) in pyridine (30.0 mL) was added p-TsCl (5.63 g, 30.0 mmol). After stirring for 16 h at room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between ethyl acetate (300.0 ml) and 1.0 N hydrochloric acid (200.0 mL) and separated. The organic layer was washed with water (2×100 mL), saturated sodium chloride (100 mL), dried (MgSO4), filtered and filtrate concentrated under reduced pressure. The residue was dissolved in DMF (100.0 mL), added to a stirred solution of 2-(tert-butyl)phenol (10.8 g, 72.0 mmol) and K3PO4 (45.8 g, 216 mmol) in DMF (60.0 mL) and the resulting reaction mixture was heated at 80° C. for 16 h. Then, the reaction mixture was cooled to room temperature, poured into water (150.0 mL) and extracted with ethyl acetate (2×100.0 mL). The combined organics were washed with water (2×150 ml), saturated sodium chloride (100 mL), dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, 95:5 to 90:10 hexane/ethyl acetate) to provide tert-butyl 4-[2-(2-tert-butylphenoxy)ethyl]piperidine-1-carboxylate (31.7 g, 44%) as a yellow oil.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. customthe resulting residue was partitioned between ethyl acetate (300.0 ml) and 1.0 N hydrochloric acid (200.0 mL)
  3. customseparated
  4. washThe organic layer was washed with water (2×100 mL), saturated sodium chloride (100 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationfiltrate concentrated under reduced pressure
  8. dissolutionThe residue was dissolved in DMF (100.0 mL)
  9. customthe resulting reaction mixture
  10. temperaturewas heated at 80° C. for 16 h
  11. temperatureThen, the reaction mixture was cooled to room temperature
  12. extractionextracted with ethyl acetate (2×100.0 mL)
  13. washThe combined organics were washed with water (2×150 ml), saturated sodium chloride (100 mL)
  14. dry with materialdried (MgSO4)
  15. filtrationfiltered
  16. concentrationconcentrated under reduced pressure
  17. customThe residue was purified by flash column chromatography (silica gel, 95:5 to 90:10 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-f1dfaa9d9a174b849aee7b5fb7eff5a8
Source dataset
uspto-grants-2013_11
Patent number
US08586571B2

Reaction notes

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