Ethylene Glycol → 5-(4-Chlorophenyl)-6-(2-hydroxyethoxy)nicotinic acid

HRID 1528403Notes

Reaction equation

HRID 1528403 reaction equation
[CH2:1]([OH:4])[CH2:2][OH:3].[H-].[Na+].Cl[C:8]1[N:13]=[CH:12][C:11]([C:14]([OH:16])=[O:15])=[CH:10][C:9]=1[C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1.O>CN(C=O)C>[Cl:23][C:20]1[CH:19]=[CH:18][C:17]([C:9]2[C:8]([O:3][CH2:2][CH2:1][OH:4])=[N:13][CH:12]=[C:11]([CH:10]=2)[C:14]([OH:16])=[O:15])=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 962WaterHCID 24758Sodium hydride2×HCID 866191836-Chloro-5-(4-chlorophenyl)-3-pyridinecarboxylic acid

Product 1

HCID 666786215-(4-Chlorophenyl)-6-(2-hydroxyethoxy)nicotinic acidYield 41.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of ethane-1,2-diol (301 mg, 270 μA, 4.84 mmol) in dried DMF (6 mL) was added sodium hydride (232 mg, 4.84 mmol) and the reaction mixture was stirred at room temperature for 15 minutes. The resulting solution was added slowly to a solution of 6-chloro-5-(4-chlorophenyl)-3-pyridinecarboxylic acid (CAN 1012792-56-1; 0.590 g, 2.2 mmol) in dried DMF (6 mL) and stirred at 80° C. for 4 h. More sodium hydride (106 mg, 2.2 mmol) was added and at room temperature and stirring at 80° C. commenced for another 2 h. Water was added and DMF was evaporated. The residue was dissolved in water; acidified with 3M HCl to pH 3. The suspension was filtered; the filter cake was washed with water and dried under high vacuo. The crude material was purified by flash chromatography (ReproFlash Acidosil-S, 50 g, 50% to 100% ethylacetate in heptane) to give 0.27 g (41%) of the title compound as a white solid; MS (ESI): 292.1 (M−H)−.

Workup

  1. stirringstirred at 80° C. for 4 h
  2. stirringstirring at 80° C.
  3. waitcommenced for another 2 h
  4. customDMF was evaporated
  5. dissolutionThe residue was dissolved in water
  6. filtrationThe suspension was filtered
  7. washthe filter cake was washed with water
  8. customdried under high vacuo
  9. customThe crude material was purified by flash chromatography (ReproFlash Acidosil-S, 50 g, 50% to 100% ethylacetate in heptane)

Sources & evidence

ORD record
ord-14860a738228443eac8078d40384b7c1
Source dataset
uspto-grants-2015_07
Patent number
US09090599B2

Reaction notes

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