Reaction #40262

Reaction equation

2-chloro-1-methylpyridinium iodide

(1,4-dioxaspiro[4.5]dec-7-en-8-yl) acetic acid

triethylamine

2-iodo-6-methoxyaniline

→

2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-N-(2′-iodo-6′-methoxy-phenyl)acetamide

Yield 89.6%

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

Yield 89.6%

Solvents

dichloromethane

Conditions

Workup

1. 1
   TemperatureThe reaction mixture is heated
2. 2
   Temperatureat reflux for 20 hours
3. 3
   TemperatureAfter cooling
4. 4
   Extractionacidification with 1N HCl solution to pH=5-6, the mixture is extracted with dichloromethane
5. 5
   WashThe organic phases are washed with saturated aqueous sodium chloride solution
6. 6
   Dryingdried over magnesium sulfate
7. 7
   Otherevaporated under vacuum
8. 8
   OtherPurification by flash chromatography on silica gel (eluent: heptane/ethyl acetate 4/6)

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 1N HCl solution to pH=5-6, the mixture is extracted with dichloromethane. 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-dioxaspiro[4.5]dec-7-en-8-yl)-N-(2′-iodo-6′-methoxy-phenyl)acetamide (16) in the form of a yellow foam (yield: 90%).

Source