Sodium Iodide → Ethyl (4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)carboxylate

HRID 2406369Notes

Reaction equation

HRID 2406369 reaction equation
[I-:1].[Na+].C(Cl)(=O)C.Cl[C:8]1[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:12]([CH3:19])[N:11]=[C:10]2[S:20][C:21]3[CH2:26][CH2:25][CH2:24][CH2:23][C:22]=3[C:9]=12>C(#N)C>[I:1][C:8]1[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:12]([CH3:19])[N:11]=[C:10]2[S:20][C:21]3[CH2:26][CH2:25][CH2:24][CH2:23][C:22]=3[C:9]=12

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 6367Acetyl chlorideHCID 15485209Ethyl 4-chloro-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridine-3-carboxylate

Product 1

HCID 66603576Ethyl (4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)carboxylateYield 78.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Sodium iodide (994.0 g, 6.63 Mol) was added over 5 minutes to a stirred solution of acetyl chloride (177 mL, 2.48 Mol) and ethyl (4-chloro-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridine-3-yl)carboxylate (Preparation 4, 257 g, 0.83 Mol) in acetonitrile (2.0 L) at room temperature. The resulting mixture was heated to reflux and stirred for 30 hours. The mixture was allowed to cool to room temperature and stood for 72 hours. The solids were collected by filtration and washed with cold acetonitrile (500 mL). The solids were partitioned between dichloromethane (1.5 L) and water (0.75 L). The aqueous layer was basified to pH 9 by addition of 2 M sodium hydroxide solution and the two layers were separated. The organic layer was washed with 2 M sodium thiosulphate solution (800 mL), brine (800 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to give the title compound (260.0 g, 78%) as a beige solid. This material was determined by 1H NMR spectroscopy to be a 13:1 mixture of ethyl (4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridine-3-yl)carboxylate and ethyl (4-chloro-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridine-3-yl)carboxylate respectively.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux
  3. waitstood for 72 hours
  4. filtrationThe solids were collected by filtration
  5. washwashed with cold acetonitrile (500 mL)
  6. customThe solids were partitioned between dichloromethane (1.5 L) and water (0.75 L)
  7. additionThe aqueous layer was basified to pH 9 by addition of 2 M sodium hydroxide solution
  8. customthe two layers were separated
  9. washThe organic layer was washed with 2 M sodium thiosulphate solution (800 mL), brine (800 mL)
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d73b2fc24cd443eca1e7d7e59c9982a4
Source dataset
uspto-grants-2014_08
Patent number
US08809363B2

Reaction notes

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