Mechlorethamine → 1-Methyl-4-phenylpiperidine-4-carbonitrile

HRID 1992719Notes

Reaction equation

HRID 1992719 reaction equation
[CH3:1][N:2]([CH2:6][CH2:7]Cl)[CH2:3][CH2:4]Cl.[CH2:9]([C:16]#[N:17])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[NH2-].[Na+]>C1(C)C=CC=CC=1>[CH3:1][N:2]1[CH2:6][CH2:7][C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)([C:16]#[N:17])[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 4033MechlorethamineHCID 8794PhenylacetonitrileHCID 24533Sodium amide

Product 1

HCID 625131-Methyl-4-phenylpiperidine-4-carbonitrileYield 58.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of mechlorethamine (4 g, 25.6 mmol) and benzyl cyanide (4 g, 34.2 mmol) in toluene (25 ml) was added sodium amide (2 g, 51.2 mmol) at 40-50° C. in portions for 1 hour. The reaction mixture was heated to reflux about 2 hours after the addition. The reaction mixture was cooled to room temperature and washed with saturated sodium bicarbonate solution and brine, dried over sodium sulfate and concentrated. The residue was applied to flash column chromatography using methylene chloride and methanol (100:5) as eluents to give 3 g of desired product.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux about 2 hours
  3. additionafter the addition
  4. washwashed with saturated sodium bicarbonate solution and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-a6b5865b77124f84a75bcab02018e967
Source dataset
uspto-grants-2010_01
Patent number
US07649092B2

Reaction notes

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