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

HRID 2224131Notes

Reaction equation

HRID 2224131 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-b78b2f7c767a4518b18f926a213bdd64
Source dataset
uspto-grants-2008_05
Patent number
US07378420B2

Reaction notes

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