Sodium hydride → 4-[2-(4-Methoxybenzyloxy)ethyl]piperidine

HRID 2095455

Reaction equation

HRID 2095455 reaction equation
[H-].[Na+].C(OC([N:10]1[CH2:15][CH2:14][CH:13]([CH2:16][CH2:17][OH:18])[CH2:12][CH2:11]1)=O)(C)(C)C.Br[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1>C1COCC1>[CH3:28][O:27][C:24]1[CH:25]=[CH:26][C:21]([CH2:20][O:18][CH2:17][CH2:16][CH:13]2[CH2:12][CH2:11][NH:10][CH2:15][CH2:14]2)=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1650214-Methoxybenzyl bromideHCID 8541401-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidine

Product 1

HCID 568305684-[2-(4-Methoxybenzyloxy)ethyl]piperidineYield 53.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

NaH (60% dispersion in oil, 98 mg, 2.4 mmol, 1.2 equiv.) was added to a solution of 1-(tert-butoxycarbonyl)-4-(2-hydroxyethyl)piperidine (468 mg, 2.0 mmol) in THF (10 mL) at 0° C. under Ar protection. The mixture was warmed to room temperature and stirred at that temperature for 3 h. 1-(Bromomethyl)-4-methoxybenzene (353 μL, 2.4 mmol, 1.2 equiv.) was added at room temperature. After stirring for 20 h, the reaction was quenched with saturated aqueous NH4Cl solution. The mixture was extracted three times with EtOAc, and the combined organic layers were washed with brine and dried over Na2SO4. The solvent was removed, and the residue was purified by CC (SiO2, hexane/EtOAc 10:1 to 4:1) to afford the product (268 mg, 38%) as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ 7.22 (d, 2H, J=8.4 Hz), 6.85 (d, 2H, J=8.8 Hz), 4.40 (s, 2H), 4.05 (m, 2H), 3.76 (m, 4H), 3.45 (t, 2H, J=6.0 Hz), 2.65 (m, 2H), 1.62-1.50 (m, 5H), 1.44 (s, 9H), 1.08 (m, 2H).

Workup

  1. stirringAfter stirring for 20 h
  2. customthe reaction was quenched with saturated aqueous NH4Cl solution
  3. extractionThe mixture was extracted three times with EtOAc
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. customThe solvent was removed
  7. customthe residue was purified by CC (SiO2, hexane/EtOAc 10:1 to 4:1)

Sources & evidence

ORD record
ord-44d972a8dfec4b2db08071833c126c58
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Linked notes

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