Reaction #7153

Reaction equation

Intermediate 1

4-hydroxy-N-(3-iodophenyl)-3-methoxyphenylacetamide

potassium hydroxide

tetrabutylammonium hydroxide

→

desired compound

4-[2-(tert-butoxycarbonylamino)ethoxy]-N-(3-iodophenyl)-3-methoxyphenylacetamide

Solvents

1,2-dibromethane

Conditions

Workup

1. 1
   Temperatureis heated
2. 2
   WashThe reaction solution is washed with water
3. 3
   Dryingthe organic layer is dried over sodium sulfate
4. 4
   Otherthe solvent is evaporated under reduced pressure
5. 5
   workup.DISSOLUTIONThe residue is dissolved in dimethylformamide (45 ml)
6. 6
   workup.ADDITIONis added potassium phthalimide (1.9 g)
7. 7
   workup.STIRRINGThe mixture is stirred at 50° C. for 18 hours
8. 8
   workup.ADDITIONThe reaction solution is poured into ice-water
9. 9
   Extractionthe mixture is extracted with chloroform
10. 10
    WashThe extract is washed with water
11. 11
    Otherthe solvent is evaporated under reduced pressure
12. 12
    workup.DISSOLUTIONThe residue is dissolved in ethanol (50 ml)
13. 13
    workup.ADDITIONis added hydrazine monohydrate (600 mg)
14. 14
    Temperatureheated
15. 15
    Temperatureunder reflux for 3 hours
16. 16
    OtherThe insoluble materials are removed by filtration
17. 17
    Concentrationthe filtrate is concentrated
18. 18
    Extractionextracted with chloroform
19. 19
    Washwashed with water
20. 20
    Otherthe solvent is evaporated under reduced pressure
21. 21
    workup.DISSOLUTIONThe residue is dissolved in chloroform (50 ml)
22. 22
    workup.ADDITIONis added di-tert-butyl dicarbonate (4.3 g)
23. 23
    workup.STIRRINGThe mixture is stirred at 25° C. for 18 hours
24. 24
    Otherthe solvent is evaporated under reduced pressure
25. 25
    OtherThe residue is purified by silica gel column chromatography (eluent: gradient from 0% to 100% hexane/ethyl acetate)

Procedure

A mixture of Intermediate 1 (8.4 g), 1,2-dibromethane (160 ml), 40% aqueous potassium hydroxide solution (45 ml) and 40% aqueous tetrabutylammonium hydroxide solution (4.5 ml) is heated with stirring at 40° C. for 18 hours. The reaction solution is washed with water, and the organic layer is dried over sodium sulfate, and the solvent is evaporated under reduced pressure. The residue is dissolved in dimethylformamide (45 ml), and thereto is added potassium phthalimide (1.9 g). The mixture is stirred at 50° C. for 18 hours. The reaction solution is poured into ice-water, and the mixture is extracted with chloroform. The extract is washed with water, and the solvent is evaporated under reduced pressure. The residue is dissolved in ethanol (50 ml), and thereto is added hydrazine monohydrate (600 mg), and heated under reflux for 3 hours. The insoluble materials are removed by filtration, and the filtrate is concentrated, extracted with chloroform, washed with water, and the solvent is evaporated under reduced pressure. The residue is dissolved in chloroform (50 ml) and thereto is added di-tert-butyl dicarbonate (4.3 g). The mixture is stirred at 25° C. for 18 hours, and the solvent is evaporated under reduced pressure. The residue is purified by silica gel column chromatography (eluent: gradient from 0% to 100% hexane/ethyl acetate) to give the desired compound (5.2 g).

Source