Dimethylformamide → 6-(4-hydroxypiperidin-1-yl)pyridine-3-carbonitrile

HRID 1808739Notes

Reaction equation

HRID 1808739 reaction equation
CN(C)C=O.Cl[C:7]1[CH:12]=[CH:11][C:10]([C:13]#[N:14])=[CH:9][N:8]=1.[OH:15][CH:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.C(=O)([O-])[O-].[K+].[K+]>O>[OH:15][CH:16]1[CH2:21][CH2:20][N:19]([C:7]2[N:8]=[CH:9][C:10]([C:13]#[N:14])=[CH:11][CH:12]=2)[CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 79341Piperidin-4-olHCID 51520946-Chloro-3-pyridinecarbonitrile

Product 1

HCID 247031516-(4-hydroxypiperidin-1-yl)pyridine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a N,N-dimethylformamide (100 mL) solution of 2-chloro-5-cyanopyridine (36.2 g, 262 mmol) and 4-hydroxypiperidine (27.9 g, 275 mmol) was added potassium carbonate (40.1 g, 290 mmol). The reaction mixture was heated to 100° C. and stirred for 3 hours. It was cooled to room temperature, diluted with water (400 mL), and extracted with dichloromethane (3×250 mL). The combined organic extracts were washed with brine, dried (magnesium sulfate), and concentrated in vacuo to afford the title compound as a solid. This crude product was used in the subsequent step without further purification. 1H NMR (500 MHz, CDCl3) δ 8.39 (d, J=2.3 Hz, 1H), 7.58 (dd, J=9.1, 2.4 Hz, 1H), 6.62 (d, J=9.1 Hz, 1H), 4.10 (dt, J=13.6, 5.0 Hz, 2H), 4.01 (tt, J=8.3, 3.9 Hz, 1H), 3.37 (ddd, J=13.6, 9.2, 3.4 Hz, 2H), 2.61 (s, 1H), 1.99-1.92 (m, 2H), 1.62-1.53 (m, 2H); LC-MS: m/z 204.2 (M+H).

Workup

  1. temperatureIt was cooled to room temperature
  2. extractionextracted with dichloromethane (3×250 mL)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried (magnesium sulfate)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b59f16f1128d4765b9dd2ca23580e2dd
Source dataset
uspto-grants-2013_01
Patent number
US08361994B2

Reaction notes

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