Methanesulfonic Acid → 1-(3-Chloropyridin-2-yl)-4-hydroxypiperidine-4-carbonitrile

HRID 404566Notes

Reaction equation

HRID 404566 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[Si]([C:19]#[N:20])(C)(C)C.[Al+3].[Cl-].[Cl-].[Cl-].CS(O)(=O)=O>C1(C)C=CC=CC=1.O>[Cl:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][C:11]([OH:14])([C:19]#[N:20])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6395Methanesulfonic AcidHCID 82115Trimethylsilyl cyanideHCID 6451240Aluminum(III) ChlorideHCID 247108361-(3-Chloropyridin-2-yl)piperidin-4-one2×

Product 1

HCID 714170321-(3-Chloropyridin-2-yl)-4-hydroxypiperidine-4-carbonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A solution of N-(3-chloro-2-pyridyl)-4-piperidone (compound 21) (13 g, 62 mmol), TMS-CN (6.2 g, 62 mmol) and AlCl3 (0.1 g) in toluene (100 ml) was heated to 60° C., and stirred overnight. Then 0.1 equivalent of methanesulfonic acid was added, and the reaction mixture was heated to reflux for half an hour. After the reaction was completed, three times of water was added into the reaction solution. The reaction mixture was extracted by ethyl acetate. The organic layer was evaporated to give a crude product, which was purified using column chromatography to give the product. (8 g, 55%)

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for half an hour
  3. extractionThe reaction mixture was extracted by ethyl acetate
  4. customThe organic layer was evaporated

Sources & evidence

ORD record
ord-6f10464bd3bf435a8bb3b86ef05842dc
Source dataset
uspto-grants-2014_06
Patent number
US08748610B2

Reaction notes

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