Pyridine → HCID 23353317, compound

HRID 235069Notes

Reaction equation

HRID 235069 reaction equation
C([C:3]1[C:8](O)=[CH:7][CH:6]=[CH:5][N:4]=1)#N.[H-].[Na+].Br[CH2:13][C:14]([O:16][CH2:17]C)=[O:15].[N:19]1[CH:24]=CC=CC=1.CC(C)([O-:28])C.[K+]>CN(C=O)C.C1COCC1>[NH2:19][C:24]1[C:8]2[C:3](=[N:4][CH:5]=[CH:6][CH:7]=2)[O:28][C:13]=1[C:14]([O:16][CH3:17])=[O:15]

Participants

8

Reactant 5

HCID 1049PyridineHCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 1019203-Hydroxypyridine-2-carbonitrileHCID 23665647Potassium tert-butoxide

Product 1

HCID 23353317HCID 23353317, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

2-Cyano-3-hydroxypyridine (1.2 g, 10 mmol), prepared as described in Synthesis 316 (1983), was aedded in portions to a 0° C. suspension of NaH (0.4 g of 60% dispersion, 10 mmol) in DMF (5 mL). After stirring for 20 min at 0° C., ethyl bromoacetate was added dropwise. The reaction was stirred for 30 min at 25° C. and was the poured into ice water. The resulting solid was collected by filtration and was washed with a small portion of water. The crude ethyl ester was taken up in EtOAc, dried (MgSO4), filted, and concentrated (1.16 g obtained). To the pyridine (1.0 g, 5.0 mmol) in THF (20 mL) was added potassium t-butoxide (0.56 g, 5.0 mmol). After stirring for 45 min, the reaction was partitioned between EtOAc and NaHCO3 solution. The layers were seperated and the aqueous layer was extracted with EtOAc (2x). The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated to provide 0.76 g (76%) of the title compound: 1H NMR (300 MHz, CDCl3) δ1.46 (t, 3H), 4.47 (q, 2H), 5.21 (bs, 2H), 7.38 (dd, 1H), 7.76 (dd, 1H), 8.56 (dd, 1H).

Workup

  1. customas described in Synthesis 316 (1983)
  2. customwas aedded in portions to a 0° C.
  3. stirringThe reaction was stirred for 30 min at 25° C.
  4. filtrationThe resulting solid was collected by filtration
  5. washwas washed with a small portion of water
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. custom(1.16 g obtained)
  9. stirringAfter stirring for 45 min
  10. customthe reaction was partitioned between EtOAc and NaHCO3 solution
  11. customThe layers were seperated
  12. extractionthe aqueous layer was extracted with EtOAc (2x)
  13. washThe combined organic layers were washed with brine
  14. dry with materialdried (MgSO4)
  15. filtrationfiltered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-f816e63913d74a609a9e0febd471f055
Source dataset
uspto-grants-1997_01
Patent number
US05597823

Reaction notes

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