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

HRID 1949727Notes

Reaction equation

HRID 1949727 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-27607c6a96524a10b37de97058ca1071
Source dataset
uspto-grants-2013_03
Patent number
US08399690B2

Reaction notes

Loading…