Sodium hydride → Pyridin-3-yl-(pyridin-2-yloxy)-acetic acid ethyl ester

HRID 352226

Reaction equation

HRID 352226 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1.[CH2:10]([O:12][C:13](=[O:22])[CH:14](Br)[C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1)[CH3:11]>CN(C=O)C>[CH2:10]([O:12][C:13](=[O:22])[CH:14]([C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1)[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1)[CH3:11]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 21985933Ethyl 2-bromo-2-(pyridin-3-yl)acetateHCID 178516071HCID 178516071, compound

Product 1

HCID 69848905Pyridin-3-yl-(pyridin-2-yloxy)-acetic acid ethyl esterYield 3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (520 mg; 21.8 mmol; 1.4 equiv) was stirred with 2-hydroxypyridine (1.73 g; 18.2 mmol; 1.2 equiv) in DMF (30 mL) for 15 min. This solution was added to an aliquot of bromo-pyridin-3-yl-acetic acid ethyl ester (approx. 3.6 g; 15 mmol) in DMF (20 mL). After stirring overnight, at rt., the resulting opaque black solution was concentrated in vacuo, dissolved in 20% isopropyl alcohol/chloroform, washed 5 times with saturated NaHCO3(aq), washed twice with saturated NaCl(aq), and dried over Na2SO4(s). After filtration, the solution was concentrated in vacuo and purified by SiO2 column chromatography on two consecutive columns with a 1% methanol/chloroform mobile phase and then an ethyl acetate/hexanes mobile phase (30%, 40%, 50% step gradient). A light yellow oil (134 mg; approx. 3% yield) was isolated. MS(ES) calc'd: [M+H]+=259.2 m/z. Found: 259.1 m/z.

Workup

  1. concentration, the resulting opaque black solution was concentrated in vacuo
  2. dissolutiondissolved in 20% isopropyl alcohol/chloroform
  3. washwashed 5 times with saturated NaHCO3(aq)
  4. washwashed twice with saturated NaCl(aq)
  5. dry with materialdried over Na2SO4(s)
  6. filtrationAfter filtration
  7. concentrationthe solution was concentrated in vacuo
  8. custompurified by SiO2 column chromatography on two consecutive columns with a 1% methanol/chloroform mobile phase
  9. customA light yellow oil (134 mg; approx. 3% yield) was isolated

Sources & evidence

ORD record
ord-d94fa65d735a4eb0a54115991fc4408a
Source dataset
uspto-grants-2004_06
Patent number
US06743794B2

Linked notes

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