Propanoic acid, 2-bromo-2-methyl-, ethyl ester → 2-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxy)-2-methyl-propionic acid ethyl ester

Participants

Reaction Steps

A mixture of 3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenol [945 mg, 2.42 mmol, Example 35(i)], PS-TBD (3.38 g, 5 mmol), ethyl 2-bromoisobutyrate (888 mL, 605 mmol) and acetonitrile (20 mL) is heated to reflux and stirred for 2 hours. The heating is turned off and the mixture is stirred overnight at ambient temperature. The reaction mixture is filtered to remove the resin and the resin is washed with MeOH (20 mL) and with acetonitrile (20 mL). The combined filtrate and washings are concentrated by rotary evaporator. The residue is subjected to flash column chromatography on silica (40 g) eluting with 20 to 50% EtOAc in heptane gradient to afford 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenoxy)-2-methyl-propionic acid ethyl ester [450 mg, 37%, Example 42] as a solid. LCMS: RT=2.9 minutes, MS: 504 (M+H).

Provenance & Evidence