Sodium hydride → 1-(Tert-butoxycarbonyl)-4-[2-(4-fluorobenzyloxy)ethyl]piperidine

HRID 2095446Notes

Reaction equation

HRID 2095446 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][OH:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[F:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24]Br)=[CH:22][CH:21]=1>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][O:16][CH2:24][C:23]2[CH:26]=[CH:27][C:20]([F:19])=[CH:21][CH:22]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromideHCID 8541401-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidine

Product 1

HCID 593714721-(Tert-butoxycarbonyl)-4-[2-(4-fluorobenzyloxy)ethyl]piperidineYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(tert-butoxycarbonyl)-4-(2-hydroxyethyl)piperidine (195 mg, 0.85 mmol) in THF (5 mL) was added sodium hydride (60% dispersion in oil, 41 mg, 1.02 mmol, 1.2 equiv.). After stirring at room temperature for 2 h, 4-fluorobenzyl bromide (127 μL, 1.02 mmol, 1.2 equiv.) was added. The reaction mixture was allowed to stand overnight. After quenching with H2O, the phases were separated, and the aqueous layer was extracted with EtOAc. The combined organic layer was washed with brine and dried over Na2SO4. After the solvent was removed, the residue was purified by CC (SiO2, hexane/EtOAc 4:1) to afford 1-(tert-butoxycarbonyl)-4-[2-(4-fluorobenzyloxy)ethyl]piperidine (257 mg, 90%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.28 (dd, 2H, J=8.0 Hz, J=5.2 Hz), 7.01 (t, 2H, J=8.4 Hz), 4.61 (s, 2H), 4.05 (d, 2H, J=12.8 Hz), 3.48 (t, 2H, J=6.0 Hz), 2.66 (t, 2H, J=12.4 Hz), 1.55 (m, 5H), 1.44 (s, 9H), 1.10 (m, 2H).

Workup

  1. waitto stand overnight
  2. customAfter quenching with H2O
  3. customthe phases were separated
  4. extractionthe aqueous layer was extracted with EtOAc
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. customAfter the solvent was removed
  8. customthe residue was purified by CC (SiO2, hexane/EtOAc 4:1)

Sources & evidence

ORD record
ord-6f95c73b9bc944fba08d707e3594092e
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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