Picolinic acid → Ethyl 1,5-naphthyridin-3-ylacetate

HRID 82230Notes

Reaction equation

HRID 82230 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[N:9][CH:8]=[CH:7][CH:6]=2.C([C:14](CC)([C:18]([O-:20])=[O:19])C([O-])=O)C.C(=O)([O-])[O-].[Cs+].[Cs+].N1C=CC=[CH:31][C:30]=1C(O)=O>O1CCOCC1.C(OCC)(=O)C.[Cu]I>[N:4]1[C:5]2[C:10](=[N:9][CH:8]=[CH:7][CH:6]=2)[CH:11]=[C:2]([CH2:14][C:18]([O:20][CH2:30][CH3:31])=[O:19])[CH:3]=1

Participants

8

Reactant 4

HCID 1018Picolinic acidHCID 10796Cesium carbonateHCID 69515632,2-DiethylpropanedioateHCID 128788183-Bromo-1,5-naphthyridine

Product 1

HCID 70817520Ethyl 1,5-naphthyridin-3-ylacetateYield 402.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 3-bromo-1,5-naphthyridine (540 mg, 2.58 mmol), diethylmalonate (0.8 mL, 5.17 mmol) and cesium carbonate (2.53 g, 7.75 mmol) in 1,4-dioxane (6 mL) was degassed with argon for 15 min then picolinic acid (64 mg, 0.517 mmol) and CuI (50 mg, 0.258 mmol) was added. The mixture was heated in a sealed tube at 110° C. for 24 hours then cooled to room temperature, diluted with ethyl acetate (10 mL), washed with water (10 mL) and brine (10 mL). The organic phase was dried over sodium sulphate then evaporated in vacuo and purified by column chromatography on silica gel (hexane:EtOAc 70:30) to afford 450 mg of ethyl 1,5-naphthyridin-3-ylacetate.

Workup

  1. customwas degassed with argon for 15 min
  2. temperaturethen cooled to room temperature
  3. washwashed with water (10 mL) and brine (10 mL)
  4. dry with materialThe organic phase was dried over sodium sulphate
  5. customthen evaporated in vacuo
  6. custompurified by column chromatography on silica gel (hexane:EtOAc 70:30)

Sources & evidence

ORD record
ord-dbf074aa3cb349a3be97092eb8999ff6
Source dataset
uspto-grants-2014_09
Patent number
US08846698B2

Reaction notes

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