Phosphorus oxychloride → 6-Methyl-N,N-dicyclopentylnicotinamide

HRID 981053

Reaction equation

HRID 981053 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.[CH:11]1([NH:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[CH2:15][CH2:14][CH2:13][CH2:12]1.P(Cl)(Cl)(Cl)=O>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:16]([CH:17]2[CH2:18][CH2:19][CH2:20][CH2:21]2)[CH:11]2[CH2:12][CH2:13][CH2:14][CH2:15]2)=[O:8])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 1378606-Methylnicotinic acidHCID 247671Dicyclopentylamine

Product 1

HCID 200716326-Methyl-N,N-dicyclopentylnicotinamideYield 44.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a suspension of 6-methylnicotinic acid (1.37 g, 10 mmol) in toluene (10 ml), N,N-dicyclopentylamine (1.84 g, 12 mmol) was added To the homogenous solution obtained, phosphorus oxychloride (0.23 mL, 12 mmol) was injected in dropwise fashion. The reaction mixture was then immersed in an oil-bath at 130° C. and refluxed for 8 h. The reaction flask was cooled and stirred at room temperature. After 16h, the reaction was quenched with water and extracted in ethyl acetate. The organic layer was successively washed with aq. potassium carbonate, water and brine. After drying (MgSO4), the solvent was removed. The crude product (2.5 g) was chromatographed (silica gel, ethyl acetate/acetonitrile 100/1.5) to give the title compound (1.2 g, 44%). IR (KBr)1625, 1590, 1450, 1430, 1375, 1340, 1290, 1130, 840, 750 cm-1 ; 1H NMR (CDCl3) 1.4-2.35 (m, 16H), 2.57 (s, 3H), 3.6-3.9 (m,2H), 7.17 (d, J=8 Hz, 1H), 7.6 (dd,J=3,8 Hz, 1H), and 8.5 ppm (d,J=3 Hz,1H).

Workup

  1. additionwas added To the homogenous solution
  2. customobtained
  3. customThe reaction mixture was then immersed in an oil-bath at 130° C.
  4. temperaturerefluxed for 8 h
  5. temperatureThe reaction flask was cooled
  6. customAfter 16h, the reaction was quenched with water
  7. extractionextracted in ethyl acetate
  8. washThe organic layer was successively washed with aq. potassium carbonate, water and brine
  9. dry with materialAfter drying (MgSO4)
  10. customthe solvent was removed
  11. customThe crude product (2.5 g) was chromatographed (silica gel, ethyl acetate/acetonitrile 100/1.5)

Sources & evidence

ORD record
ord-e957701b38974072ae9583c99c4acedf
Source dataset
uspto-grants-1991_02
Patent number
US04990518

Linked notes

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