Reaction #7178

Reaction equation

ethyl acetate

Intermediate 4

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

3-methylvinylbenzene

tris(2-methylphenyl)phosphine

→

4-[2-(tert-butoxycarbonylamino)-ethoxy]-3-methoxy-N-[3-[(E)-2-(3-methylphenyl)vinyl]phenyl]phenylacetamide

Yield 152.4%

Solvents

dimethylformamide

Conditions

Workup

1. 1
   Temperaturethe mixture is heated
2. 2
   Washthe mixture is washed with water and 2 M hydrochloric acid
3. 3
   DryingThe organic layer is dried over sodium sulfate
4. 4
   Otherthe solvent is evaporated under reduced pressure
5. 5
   OtherThe residue is purified by silica gel column chromatography (eluent: gradient from 0% to 100% hexane/ethyl acetate)

Procedure

Intermediate 4 (1 g) is dissolved in dimethylformamide (10 ml), and thereto are added 3-methylvinylbenzene (826 mg), palladium (II) acetate (105 mg), tris(2-methylphenyl)phosphine (143 mg), tetra-n-butyl ammonium chloride (130 mg), and the mixture is heated with stirring at 97° C. for 18 hours under argon atmosphere. To the reaction solution is added ethyl acetate, and the mixture is washed with water and 2 M hydrochloric acid. The organic layer is dried over sodium sulfate, 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 4-[2-(tert-butoxycarbonylamino)-ethoxy]-3-methoxy-N-[3-[(E)-2-(3-methylphenyl)vinyl]phenyl]phenylacetamide (370 mg). This product is treated with 10% hydrogen chloride-methanol to give the desired compound (120 mg).

Source