Triethylamine → 2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-N-(2'-iodo-6'-methoxyphenyl)acetamide

HRID 2215641Notes

Reaction equation

HRID 2215641 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][C:8]([CH2:11][C:12]([OH:14])=O)=[CH:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[I:15][C:16]1[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[C:17]=1[NH2:18].[I-].ClC1C=CC=C[N+]=1C.C(N(CC)CC)C>ClCCl>[O:4]1[C:5]2([CH2:10][CH2:9][C:8]([CH2:11][C:12]([NH:18][C:17]3[C:19]([O:23][CH3:24])=[CH:20][CH:21]=[CH:22][C:16]=3[I:15])=[O:14])=[CH:7][CH2:6]2)[O:1][CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 1670692-Chloro-1-methylpyridinium iodideHCID 112870902-(1,4-Dioxaspiro[4.5]dec-7-en-8-yl)acetic acidHCID 113796632-Iodo-6-methoxyaniline

Product 1

HCID 219516902-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-N-(2'-iodo-6'-methoxyphenyl)acetamideYield 89.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (1,4-dioxaspiro[4.5]dec-7-en-8-yl) acetic acid (567 mg; 2.86 mmol; 1 eq) (7) and 2-iodo-6-methoxyaniline (1 g; 2.86 mmol; 1 eq) in anhydrous dichloromethane (30 mL) is admixed with 2-chloro-1-methylpyridinium iodide (1.46 g; 5.73 mmol; 2 eq) and triethylamine (3.98 mL; 28.65 mmol; 10 eq). The reaction mixture is heated at reflux for 20 hours. After cooling and acidification with iN HCl solution to pH=5–6, the mixture is extracted with dichloro-methane. The organic phases are washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and evaporated under vacuum. Purification by flash chromatography on silica gel (eluent: heptane/ethyl acetate 4/6) gives 1.10 g of 2-(1,4-di-oxaspiro[4.5]dec-7-en-8-yl)-N-(2′-iodo-6′-methoxy-phenyl)acetamide (16) in the form of a yellow foam (yield: 90%).

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureat reflux for 20 hours
  3. temperatureAfter cooling
  4. extractionacidification with iN HCl solution to pH=5–6, the mixture is extracted with dichloro-methane
  5. washThe organic phases are washed with saturated aqueous sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. customevaporated under vacuum
  8. customPurification by flash chromatography on silica gel (eluent: heptane/ethyl acetate 4/6)

Sources & evidence

ORD record
ord-0550cd4ff98f4667864d342cd08307a1
Source dataset
uspto-grants-2006_09
Patent number
US07109327B2

Reaction notes

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