Phosphorus oxychloride → HCID 18329980, compound

HRID 2271092Notes

Reaction equation

HRID 2271092 reaction equation
O=[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][NH:5][CH:4]=[C:3]1[CH2:13][CH2:14][CH3:15].P(Cl)(Cl)([Cl:18])=O>>[Cl:18][C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[CH:4][C:3]=1[CH2:13][CH2:14][CH3:15]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 12590548HCID 12590548, compound

Product 1

HCID 18329980HCID 18329980, compoundYield 78%

Procedure

A mixture of ethyl 1,4-dihydro-4-oxo-3-propyl-5-pyridinecarboxylate (prepared from 3-oxoenanthic acid, ethyl ester as described in J. Heterocyclic Chem. 1980, 17, 359-368) (3.33 g, 15.9 mmol) and phosphorus oxychloride (50 ml) was heated at reflux for 2 h. The excess solvent was removed in vacuo and the residue was azeotroped with toluene. The residue was dissolved in dichloromethane (75 ml) and washed with saturated aqueous NaHCO3 (100 ml). The aqueous layer was further extracted with dichloromethane (2×75 ml), and the combined organic extracts were dried (Na2SO4) and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 25% EtOAc/hexane) to yield 2.84 g (78%) of the title compound as a pale yellow oil; 1H NMR (250 MHz, CDCl3) δ1.00 (3H, t, J 7.3 Hz), 1.42 (3H, t, J 7.1 Hz), 1.68 (2H, m), 2.77 (2H, m), 4.43 (2H, q, J 7.1 Hz), 8.51 (1H, s), 8.78 (1H, s); MS (ES+) m/z 228/230 [MH]+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. customThe excess solvent was removed in vacuo
  4. customthe residue was azeotroped with toluene
  5. dissolutionThe residue was dissolved in dichloromethane (75 ml)
  6. washwashed with saturated aqueous NaHCO3 (100 ml)
  7. extractionThe aqueous layer was further extracted with dichloromethane (2×75 ml)
  8. dry with materialthe combined organic extracts were dried (Na2SO4)
  9. customevaporated in vacuo
  10. customThe residue was purified by flash chromatography (silica gel, 25% EtOAc/hexane)

Sources & evidence

ORD record
ord-eed7528b96284766816b4cf746e338c2
Source dataset
uspto-grants-2001_12
Patent number
US06333336B1

Reaction notes

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