Dimethylformamide → 3-Iodo-4-(2-(thiophen-3-yl)ethoxy)pyridine

HRID 627891Notes

Reaction equation

HRID 627891 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[I:8].[S:9]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][OH:16])=[CH:10]1.O1CCCC1.CN(C)C=O.[H-].[Na+]>O>[I:8][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:2]=1[O:16][CH2:15][CH2:14][C:11]1[CH:12]=[CH:13][S:9][CH:10]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 83731Thiophene-3-ethanolHCID 27631634-Chloro-3-iodopyridine

Product 1

HCID 579002113-Iodo-4-(2-(thiophen-3-yl)ethoxy)pyridineYield 81%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 4-chloro-3-iodo-pyridine (4.79 g, 20.0 mmol) and 2-(3-thienyl)ethanol (2.43 mL, 22.0 mmol) in a mixture of tetrahydrofuran (60 mL, 700 mmol) and N,N-dimethylformamide (20 mL, 200 mmol) was added sodium hydride, 60% dispersion in mineral oil (0.960 g, 24.0 mmol) portionwise over 30 min. The mixture was stirred for 2 hours, poured carefully into 200 ml of cold water and extracted with diethylether twice. The organic extract was washed with water and brine, and dried over MgSO4. After concentration under vacuum, the crude residue was purified on silica gel column, eluting with 50% ethyl acetate in hexane to give 3-iodo-4-(2-(thiophen-3-yl)ethoxy)pyridine (yield 5.34 g, 81%). 1H NMR (400 MHz, CDCl3) δ 8.75 (s, 1H), 8.35 (d, J=5.6, 1H), 7.29 (dd, J=3.0, 4.8, 1H), 7.19 (s, 1H), 7.12 (d, J=4.9, 1H), 6.70 (d, J=5.6, 1H), 4.26 (t, J=6.5, 2H), 3.21 (t, J=6.5, 2H). MS (ESI+) 332.0, 221.9.

Workup

  1. extractionextracted with diethylether twice
  2. extractionThe organic extract
  3. washwas washed with water and brine
  4. dry with materialdried over MgSO4
  5. concentrationAfter concentration under vacuum
  6. customthe crude residue was purified on silica gel column
  7. washeluting with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-7dfd5eced4a344b8b694daafb83e5b99
Source dataset
uspto-grants-2016_04
Patent number
US09309265B2

Reaction notes

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