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

HRID 1443053Notes

Reaction equation

HRID 1443053 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-19aa3172ea1b4ed8906fba55910025a8
Source dataset
uspto-grants-2010_02
Patent number
US07659395B2

Reaction notes

Loading…