Reaction #7168

Reaction equation

phenylboronic acid

cesium carbonate

water

Intermediate 4

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

→

4-[2-(tert-butoxycarbonylamino)ethoxy]-3-methoxy-N-(3-phenylphenyl)phenylacetamide

Yield 77.3%

Solvents

tetrahydrofuran

Conditions

Workup

1. 1
   Temperaturethe mixture is heated
2. 2
   Temperatureunder reflux for 18 hours under argon atmosphere
3. 3
   OtherThe solvent is evaporated under reduced pressure
4. 4
   Otherthe residue is purified by silica gel column chromatography (eluent: gradient from 0% to 100% hexane/ethyl acetate)

Procedure

Intermediate 4 (500 mg) is dissolved in tetrahydrofuran (10 ml), and thereto are added tetrakis(triphenylphosphine)palladium (0) (110 mg), phenylboronic acid (230 mg), cesium carbonate (1.2 g) and water (2 ml), and the mixture is heated under reflux for 18 hours under argon atmosphere. The solvent is evaporated under reduced pressure, and the residue is purified by silica gel column chromatography (eluent: gradient from 0% to 100% hexane/ethyl acetate) to give 4-[2-(tert-butoxycarbonylamino)ethoxy]-3-methoxy-N-(3-phenylphenyl)phenylacetamide (350 mg). This product is treated with 10% hydrogen chloride-methanol to give the desired compound (210 mg).

Source