Methyl iodide → 1-(4-Bromo-2-(methoxymethyl)phenyl)-2-ethylpiperidine

HRID 1630981Notes

Reaction equation

HRID 1630981 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:5]=[CH:6][C:7]([N:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH:13]2[CH2:18][CH3:19])=[C:8]([CH2:10][OH:11])[CH:9]=1.[CH3:20]I>CN(C=O)C>[Br:3][C:4]1[CH:5]=[CH:6][C:7]([N:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH:13]2[CH2:18][CH3:19])=[C:8]([CH2:10][O:11][CH3:20])[CH:9]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58554150(5-Bromo-2-(2-ethylpiperidin-1-YL)phenyl)methanol

Product 1

HCID 585541651-(4-Bromo-2-(methoxymethyl)phenyl)-2-ethylpiperidineYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of sodium hydride (2.3 g, 93 mmol) in anhydrous DMF (130 mL) was added a solution of [5-bromo-2-(2-ethylpiperidin-1-yl)phenyl]methanol (15 g, 48.3 mmol) in DMF (20 mL) drop wise at 0° C. After 30 minutes, methyl iodide was added drop wise at 0° C. The reaction mixture was quenched with a saturated aqueous solution of NH4Cl (30 mL), then diluted with water (100 mL) and extracted with EtOAc. The organic layer was dried (Na2SO4) and concentrated under reduced pressure to afford the title compound as a yellow oil (15.2 g, 97%). 1H NMR (CDCl3, 400 MHz) δ 7.59 (1H, s), 7.35 (1H, d), 7.02 (1H, d), 4.49-4.59 (2H, m), 3.43 (3H, s), 2.88 (1H, d), 2.75 (1H, bs), 2.51 (1H, bs), 1.79-1.86 (2H, m), 1.62 (3H, d), 1.40 (2H, m), 0.88 (2H, m), 0.70 (3H, t).

Workup

  1. customThe reaction mixture was quenched with a saturated aqueous solution of NH4Cl (30 mL)
  2. additiondiluted with water (100 mL)
  3. extractionextracted with EtOAc
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a116a52c98034b29b195ccdcc586bcc1
Source dataset
uspto-grants-2014_07
Patent number
US08791142B2

Reaction notes

Loading…