1,2-Dimethoxyethane → 4-(2-(2-Ethoxycarbonyl-ethyl)-3-{6-[3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-methanesulfonyl-phenoxy]-hexyl}-phenoxy)-butyric acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-{2-(2-ethoxycarbonyl-ethyl)-3-[6-(3-iodo-5-methanesulfonyl-phenoxy)-hexyl]-phenoxy}-butyric acid ethyl ester (646 mg, 0.94 mmol), 1,4-benzodioxaneboronic acid (337 g, 1.87 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (103 mg, 0.14 mmol), and cesium carbonate (617 mg, 1.87 mmol) was added dimethoxyethane (15 mL) at room temperature under nitrogen atmosphere. The resulting brown reaction mixture was heated to 96° C. and stirred for 15 h at which time the TLC of the reaction mixture indicated the absence of starting material. Then, the reaction mixture was cooled to room temperature and diluted with water (50 mL) and ethyl acetate (50 mL). The two layers were separated and the aqueous layer was extracted with ethyl acetate (2×50 mL) and the combined organic extracts were washed with water (100 mL) and brine solution (100 mL). The organic layer was dried over anhydrous magnesium sulfate and filtration of the drying agent and removal of the solvent under reduced pressure gave the colored residue which was purified by using an ISCO 80 column, eluting with 5-25% ethyl acetate in hexanes to afford 4-(3-{6-[3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-methanesulfonyl-phenoxy]-hexyl}-2-(2-ethoxycarbonyl-ethyl)-phenoxy)-butyric acid ethyl ester (336 mg, 51%) as a light brown viscous oil: ES(+)-LRMS m/e calcd for C38H48O10S (M+H)+ 697.3, found 697.23.

Provenance & Evidence