Methyl iodide → N,N-dibenzyl-N-{[1-(2-methoxy-2-methylpropyl)piperidin-4-yl]methyl}amine

HRID 1743819Notes

Reaction equation

HRID 1743819 reaction equation
[H-].[Na+].[CH2:3]([N:10]([CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([CH2:25][C:26]([CH3:29])([OH:28])[CH3:27])[CH2:21][CH2:20]1)[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.I[CH3:31]>O1CCCC1.CN(C)C=O>[CH2:3]([N:10]([CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([CH2:25][C:26]([O:28][CH3:31])([CH3:29])[CH3:27])[CH2:21][CH2:20]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 222364861-{4-[(Dibenzylamino)methyl]piperidin-1-yl}-2-methylpropan-2-ol

Product 1

HCID 22236488N,N-dibenzyl-N-{[1-(2-methoxy-2-methylpropyl)piperidin-4-yl]methyl}amineYield 24.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of sodium hydride (abt. 60% in mineral oil, 342 mg, 8.6 mmol) in a mixture of tetrahydrofuran (20 mL) and N,N-dimethylformamide (10 mL) was added a solution of 1-{4-[(dibenzylamino)methyl]piperidin-1-yl}-2-methylpropan-2-ol (EXAMPLE 4, Step 4, 3.0 g, 8.2 mmol) in tetrahydrofuran (20 ml) at 0° C. Afer being stirred at the same temperature for 30 min, 0.53 mL (8.6 mmol) of iodomethane was added to the mixture. The mixture was stirred at ambient temperature for 3 days. The mixture was partitioned between ethyl acetate and water. After extraction with ethyl acetate, the combined organic phase was dried over magnesium sulfate, and concentrated. The residue was purified by flash column chromatography on amine gel eluting with hexane/ethyl acetate (100:1) to afford 0.76 g (24%) of the title compound as colorless amorphous.

Workup

  1. stirringThe mixture was stirred at ambient temperature for 3 days
  2. customThe mixture was partitioned between ethyl acetate and water
  3. extractionAfter extraction with ethyl acetate
  4. dry with materialthe combined organic phase was dried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography on amine gel
  7. washeluting with hexane/ethyl acetate (100:1)

Sources & evidence

ORD record
ord-d3908d20ec564dc0b88edab949441bdd
Source dataset
uspto-grants-2006_03
Patent number
US07012080B2

Reaction notes

Loading…