Acetone → 4-Methyl-2-oxo-6-propyl-1,2-dihydro-3-pyridinecarbonitrile

HRID 62362

Reaction equation

HRID 62362 reaction equation
C(OC(=O)CCC)C.CC(C)=O.[CH3:13][C:14](=O)[CH2:15][C:16](=O)[CH2:17][CH2:18][CH3:19].[C:22]([CH2:24][C:25]([NH2:27])=[O:26])#[N:23].N1CCCCC1>CCOCC.CCO>[CH3:13][C:14]1[CH:15]=[C:16]([CH2:17][CH2:18][CH3:19])[NH:27][C:25](=[O:26])[C:24]=1[C:22]#[N:23]

Participants

8

Reactant 5

HCID 180AcetoneHCID 7762Ethyl butyrateHCID 7898CyanoacetamideHCID 8082PiperidineHCID 237322,4-Heptanedione

Product 1

HCID 138379154-Methyl-2-oxo-6-propyl-1,2-dihydro-3-pyridinecarbonitrileYield 40%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of NaNH2 (32.5 g, 862 mmol) in anhydrous ether (500 mL) at 30° C. was added dropwise a mixture of butyric acid ethyl ester (50 g, 431 mmol) and acetone (37.5 g, 646.5 mol). After addition, the reaction mixture was stirred for 4 h. The reaction mixture was poured onto ice water with stirring. Additional ether was added, and the layers were separated. The aqueous layer was acidified to pH 5.0 with 2 N HCl and then to pH 7.5 with Na2CO3. The aqueous layer was then extracted with ether. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product, 2,4-heptanedione (20 g, 156 mmol), and 2-cyanoacetamide (13.12 g, 156 mmol) were suspended in EtOH (160 mL) at 75° C., followed by addition of piperidine (13.2 g, 156 mmol). The contents were stirred and heated at reflux for 1 h. The mixture was cooled to room temperature and filtered. The collected solid was suspended in water and stirred for 1 h. The mixture was filtered and dried to give 4-methyl-2-oxo-6-propyl-1,2-dihydro-3-pyridinecarbonitrile (11 g, 40%). LCMS E-S (M+H)=181.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.3-12.4 (br s, 1H), 6.25 (s, 1H), 3.64 (s, 3H), 2.50 (t, 2H), 1.63 (m, 2H), 0.94 (t, 3H).

Workup

  1. additionAfter addition
  2. additionThe reaction mixture was poured onto ice water
  3. stirringwith stirring
  4. customthe layers were separated
  5. extractionThe aqueous layer was then extracted with ether
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. stirringThe contents were stirred
  10. temperatureheated
  11. temperatureat reflux for 1 h
  12. filtrationfiltered
  13. stirringstirred for 1 h
  14. filtrationThe mixture was filtered
  15. customdried

Sources & evidence

ORD record
ord-a3e152722c7b45b99bcfead0d2b8bfcd
Source dataset
uspto-grants-2016_09
Patent number
US09446041B2

Linked notes

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