Ethanol → 6-Cyclopropyl-4-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile

HRID 593845Notes

Reaction equation

HRID 593845 reaction equation
C(O)C.[CH:4]1([C:7](=O)[CH2:8][C:9](=O)[CH3:10])[CH2:6][CH2:5]1.[C:13]([CH2:15][C:16]([NH2:18])=[O:17])#[N:14].N1CCCCC1>O>[CH:4]1([C:7]2[NH:18][C:16](=[O:17])[C:15]([C:13]#[N:14])=[C:9]([CH3:10])[CH:8]=2)[CH2:6][CH2:5]1

Participants

6

Reactant 4

HCID 702EthanolHCID 7898CyanoacetamideHCID 8082PiperidineHCID 110188691-Cyclopropyl-butane-1,3-dione

Product 1

HCID 671242726-Cyclopropyl-4-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

To a stirred solution of ethanol (5 mL) were added 1-cyclopropyl-1,3-butanedione (505 mg, 3.00 mmol) and cyanoacetamide (252 mg, 3.00 mmol), and the heterogenous contents heated until homogenous (ca. 75° C.). Piperidine was added (0.395 mL, 4.00 mmol) and the mixture was heated at reflux for 30 min. The reaction mixture was allowed to cool to room temperature, wherein precipitation ensued. The solid precipitate was filtered and set aside. The filtrate was concentrated in vacuo and the oily residue treated with minimal EtOAc and then 10 mL hexanes to afford a second crop of solid. The solid product crops were combined, suspended in water (7 mL), vigorously stirred, and vacuum filtered to afford 6-cyclopropyl-4-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile as a nearly white solid (380 mg, 73%). LCMS E-S (M+H)=175.1. 1H NMR (400 MHz, CDCl3) δ ppm 1.01-1.09 (m, 2H), 1.28 (dd, J=8.59, 2.27 Hz, 2H), 1.95-2.01 (m, 1H), 2.43 (s, 3H), 5.82 (s, 1H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 30 min
  3. temperatureto cool to room temperature
  4. customwherein precipitation
  5. filtrationThe solid precipitate was filtered
  6. concentrationThe filtrate was concentrated in vacuo
  7. additionthe oily residue treated with minimal EtOAc
  8. custom10 mL hexanes to afford a second crop of solid
  9. filtrationvacuum filtered

Sources & evidence

ORD record
ord-48f575e900674fc089b2f0dade265163
Source dataset
uspto-grants-2016_01
Patent number
US09242962B2

Reaction notes

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