Methyl iodide → 1-Benzyl-4-(methoxymethyl)-N-phenylpiperidin-4-amine

HRID 1380959Notes

Reaction equation

HRID 1380959 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)([CH2:14][OH:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:25]N(C)P(=O)(N(C)C)N(C)C.CI>O>[CH2:1]([N:8]1[CH2:9][CH2:10][C:11]([CH2:14][O:15][CH3:25])([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:12][CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 12679HexamethylphosphoramideHCID 24758Sodium hydrideHCID 30172301-Benzyl-4-(phenylamino)piperidine-4-methanol

Product 1

HCID 30477241-Benzyl-4-(methoxymethyl)-N-phenylpiperidin-4-amine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 72.5 g of 1-benzyl-4-anilino-4-piperidinemethanol, 11 g of sodium hydride (50% in mineral oil) and 427 g of hexamethylphosphoric triamide is stirred. Then 33 g of methyl iodide is added dropwise to the reaction mixture and the mixture is stirred overnight. The mixture is added to 2500 ml of water, extracted with six 500 ml portions of toluene, dried over anhydrous sodium sulfate and flash evaporated to give an oil. The oil is purified in a Waters Associates Prep LC/System 500, using a PrepPAK-500/SILICA column (40% ethyl acetate in hexane) to give 1-benzyl-4-methoxymethyl-4-anilinopiperidine.

Workup

  1. stirringthe mixture is stirred overnight
  2. extractionextracted with six 500 ml portions of toluene
  3. dry with materialdried over anhydrous sodium sulfate and flash
  4. customevaporated
  5. customto give an oil
  6. customThe oil is purified in a Waters Associates Prep LC/System 500

Sources & evidence

ORD record
ord-1f6177e42b9e41bdb148c423f04b9744
Source dataset
uspto-grants-1986_04
Patent number
US04584303

Reaction notes

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