Water → 1-Benzyl-4-(pyridin-2-yl)piperidine-4-carbonitrile

HRID 1860414

Reaction equation

HRID 1860414 reaction equation
Cl[CH2:2][CH2:3][N:4]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:5][CH2:6]Cl.[N:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:21][C:22]#[N:23].[OH-].[Na+].O>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[CH2:8]([N:4]1[CH2:5][CH2:6][C:21]([C:22]#[N:23])([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][N:15]=2)[CH2:2][CH2:3]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 962WaterHCID 5928N-BenzylnormechlorethamineHCID 14798Sodium HydroxideHCID 75959Pyridine-2-acetonitrile

Product 1

HCID 227252321-Benzyl-4-(pyridin-2-yl)piperidine-4-carbonitrileYield 101.6%

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
65 °C

Procedure

To a mixture of N,N-bis-(2-chloroethyl)benzylamine (Szarvasi, E., Eur. J. Med. Chem. Chem. Ther. 11(2), 115-124, 1976) (60 g, 22 mmol), 2-pyridylacetonitrile (2.51 mL, 22 mmol) and tetrabutylammonium hydrogen sulfate (0.26 g, 0.7 mmol) in toluene (10 mL), sodium hydroxide solution (2.43 g in 4.86 mL H2O) was added over a 20 minute period. The reaction mixture was heated at 65° C. for 4 hours. The reaction mixture was cooled to room temperature, 10 mL of water was added and the solution partitioned between ethyl acetate (45 mL) and water. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification of the crude product by column chromatography (hexane: EtOAc, 2:3) gave 6.2 g (87%) of the title compound as a red solid; 1H-NMR (CDCl3): δ2.05 (d, J 13.1 Hz, 2H), 2.30 (t, J=13.2 Hz, 2H), 2.48 (t, J=13.2 Hz, 2 H), 2.97 (d, J=12.1 Hz, 2 H), 3.57 (s, 2 H), 7.19-7.27 (m, 6 H), 7.30 (d, J=7.6 Hz, 1 H), 7.60 (t, J=7.6 Hz, 1 H ), 8.58 (d, J=4.6 Hz, 1 H).

Workup

  1. additionwas added over a 20 minute period
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customthe solution partitioned between ethyl acetate (45 mL) and water
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the crude product by column chromatography (hexane: EtOAc, 2:3)

Sources & evidence

ORD record
ord-2141d01177ac440e95c1341f6284f82a
Source dataset
uspto-grants-2003_03
Patent number
US06531471B2

Linked notes

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