Phenol → 1-(Tert-butoxycarbonyl)-4-(2-phenoxyethyl)piperidine

HRID 2095409Notes

Reaction equation

HRID 2095409 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15]I)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:17]1([OH:23])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][O:23][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 996PhenolHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 9974426Tert-butyl 4-(2-iodoethyl)piperidine-1-carboxylate

Product 1

HCID 588081001-(Tert-butoxycarbonyl)-4-(2-phenoxyethyl)piperidineYield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(tert-butoxycarbonyl)-4-(2-iodoethyl)piperidine (339 mg, 1.0 mmol) and phenol (188 mg, 1.0 mmol) in DMF (5 mL) was added anhydrous K2CO3 (828 mg, 6.0 mmol) at room temperature under Ar protection. After stirring overnight, the reaction mixture was poured into 2N aqueous NaOH. The mixture was extracted three times with EtOAc, and the combined organic layers were washed with brine and dried over Na2SO4. After evaporation, the residue was purified by CC (SiO2, hexane/EtOAc 8:1, then 4:1) to afford 1-(tert-butoxycarbonyl)-4-(2-phenoxyethyl)piperidine (220 mg, 72%) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 7.27 (t, 2H, J=7.6 Hz), 6.95-6.88 (m, 3H), 4.10 (m, 2H), 3.99 (t, 2H, J=6.0 Hz), 2.70 (m, 2H), 1.72-1.63 (m, 5H), 1.47 (s, 9H), 1.23-1.15 (m, 2H). 13 C NMR (CDCl3, 100 MHz) δ 158.5, 154.4, 129.0, 120.2, 144.0, 78.8, 64.8, 43.5, 35.4, 32.6, 31.7, 28.1.

Workup

  1. extractionThe mixture was extracted three times with EtOAc
  2. washthe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. customAfter evaporation
  5. customthe residue was purified by CC (SiO2, hexane/EtOAc 8:1

Sources & evidence

ORD record
ord-4b6b45a1dc394b929170a7c211d7ca20
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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