Thionyl Chloride → 1-Piperidinyl(2-(4-pyridinylamino)phenyl)methanone

HRID 64883Notes

Reaction equation

HRID 64883 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([NH:7][C:8]2[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=2[C:10]([OH:12])=O)=[CH:3][CH:2]=1.S(Cl)(Cl)=O>CN(C)C=O>[N:1]1[CH:2]=[CH:3][C:4]([NH:7][C:8]2[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=2[C:10]([N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[O:12])=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 24386Thionyl Chloride2×HCID 4101332-(4-Pyridylamino)benzoic acid

Product 1

HCID 557541-Piperidinyl(2-(4-pyridinylamino)phenyl)methanoneYield 103.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(4-Pyridinylamino)benzoic acid (244 g, 1.14 moles) was added with stirring at room temperature to 1.4 liters of thionyl chloride containing a catalytic amount (about 1.4 ml) of N,N-dimethylformamide. A mildly exothermic reaction ensued. The reaction was stirred at room temperature for 3 hours when the excess thionyl chloride was removed in vacuo. The residual oil was azeotroped twice with toluene. The yellowish gummy acid chloride was suspended in 1.5 liters of acetonitrile and 556 ml of piperidine was added with cooling (15°-20° C.) and stirring. Stirring was continued for 3 hours. The precipitated white solid was filtered and washed with a little cold acetonitrile. It was slurried once in about 2 liters of water while adjusting the pH to 9 by addition of potassium carbonate. The solid was dried and recrystallized from 2.7 liters of ethyl acetate to afford 166 g (51.6%) of 1-[2-(4-pyridinylamino)benzoyl]piperidine, m.p. 153°-156° C.

Workup

  1. customA mildly exothermic reaction
  2. customwas removed in vacuo
  3. customThe residual oil was azeotroped twice with toluene
  4. addition556 ml of piperidine was added
  5. temperaturewith cooling (15°-20° C.)
  6. stirringStirring
  7. filtrationThe precipitated white solid was filtered
  8. washwashed with a little cold acetonitrile
  9. additionby addition of potassium carbonate
  10. customThe solid was dried
  11. customrecrystallized from 2.7 liters of ethyl acetate

Sources & evidence

ORD record
ord-3fa28ad94f1d4ba59363a7bacdc7430f
Source dataset
uspto-grants-1986_09
Patent number
US04610991

Reaction notes

Loading…