p-Toluenesulfonic acid → HCID 12569395, compound

HRID 1803056Notes

Reaction equation

HRID 1803056 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.[N:18]1[CH:23]=[CH:22][C:21]([CH:24]=O)=[CH:20][CH:19]=1.[C-:26]#[N:27].[K+]>C1COCC1.O>[N:12]1([CH:24]([C:21]2[CH:22]=[CH:23][N:18]=[CH:19][CH:20]=2)[C:26]#[N:27])[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 8083MorpholineHCID 9032Potassium CyanideHCID 133894-Pyridinecarboxaldehyde

Product 1

HCID 12569395HCID 12569395, compoundYield 79.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
100 °C

Procedure

p-Toluenesulphonic acid (1.91 g, 10.1 mmol) in THF (10 mL) was treated portionwise with morpholine (1.75 g, 1.76 mL, 20.1 mmol) and 4-pyridinecarbox-aldehyde (1 g, 9.3 mmol) was added with stirring. The reaction mixture was heated at 100° C. for 2 h. After cooling to room temperature potassium cyanide (0.82 g, 12.6 mmol) was added as a slurry in water (1.5 mL) and the reaction mixture heated for 18 h at reflux. After cooling to room temperature the THF was removed in vacuo and the residue extracted with DCM, dried over sodium sulphate, concentrated, dissolved in ethyl acetate, then filtered through a pad of silica eluting with ethyl acetate. The residue was chromatographed on silica in DCM/ethyl acetate (0-100% gradient) to give the title compound (1.5 g). δH (DMSO-d6) 8.68-8.64 (2H, m), 7.49-7.46 (2H, m), 5.53 (1H, s), 3.66-3.60 (4H, m), 2.59-2.51 (2H, m), 2.43-2.35 (2H, m).

Workup

  1. additionwas added
  2. temperaturethe reaction mixture heated for 18 h
  3. temperatureat reflux
  4. customwas removed in vacuo
  5. extractionthe residue extracted with DCM
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated
  8. dissolutiondissolved in ethyl acetate
  9. filtrationfiltered through a pad of silica eluting with ethyl acetate
  10. customThe residue was chromatographed on silica in DCM/ethyl acetate (0-100% gradient)

Sources & evidence

ORD record
ord-9946cda75bb049e6938d3db5a8afa69a
Source dataset
uspto-grants-2013_01
Patent number
US08350037B2

Reaction notes

Loading…