Iodoethane → 2-Pyridin-3-yl-butyric acid ethyl ester

HRID 401598Notes

Reaction equation

HRID 401598 reaction equation
[CH2:1]([O:3][C:4](=[O:12])[CH2:5][C:6]1[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=1)[CH3:2].[H-].[Na+].[CH2:15](I)[CH3:16]>O1CCCC1>[CH2:1]([O:3][C:4](=[O:12])[CH:5]([C:6]1[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=1)[CH2:15][CH3:16])[CH3:2]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 96490Ethyl 3-pyridylacetate

Product 1

HCID 580329722-Pyridin-3-yl-butyric acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Pyridin-3-yl-acetic acid ethyl ester (22.5 g, 0.136 mol) in tetrahydrofuran (50 mL) was slowly added to a suspension of sodium hydride (60% in mineral oil, 6 g, 0.4 mol) in tetrahydrofuran (50 mL) at 0° C. A solution of ethyl iodide (23.4 g, 0.150 mol) in tetrahydrofuran (50 mL) was added to and the reaction mixture was allowed to stir overnight at room temperature. The mixture was poured into ice and the aqueous layer was extracted three times with ethyl acetate. The organic layer washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, and evaporated to dryness. The crude residue was purified by preparative reverse phase liquid chromatography (13.5 g, 0.0699 mol, 51.3%). ESI-MS m/z calc. 193.1. found 194.2 (M+1)+ 1H NMR (CDCl3) δ: 9.42-9.39 (m, 2H), 8.58-8.55 (m, 1H), 8.17-8.13 (m, 1H), 5.09-4.97 (m, 2H), 4.35 (t, 1H, J=7.6 Hz), 3.04-2.95 (m, 1H), 2.74-2.65 (m, 1H), 2.10 (t, 3H, J=7.2 Hz), 1.79 (t, 3H, J=7.6 Hz).

Workup

  1. additionThe mixture was poured into ice
  2. extractionthe aqueous layer was extracted three times with ethyl acetate
  3. washThe organic layer washed with a saturated aqueous solution of sodium chloride
  4. dry with materialdried over sodium sulfate
  5. customevaporated to dryness
  6. customThe crude residue was purified by preparative reverse phase liquid chromatography (13.5 g, 0.0699 mol, 51.3%)

Sources & evidence

ORD record
ord-7eefddc256b44f47a272c229db1e8bdc
Source dataset
uspto-grants-2014_06
Patent number
US08741939B2

Reaction notes

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