1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → {[3-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-benzoyl]-methyl-amino}-acetic acid ethyl ester

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Reaction Steps

A solution of 3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-benzoic acid (20 g, 54 mmol), DIEA (38 mL, 216 mmol), EDCI (15.47 g, 81 mmol) and HOAT (11 g, 81 mmol) in methylene chloride (800 mL) was stirred at room temperature for 1 h, followed by addition of N-methyl glycine ethyl ester hydrochloride (12.44 g, 81 mmol). The resulting mixture was stirred at room temperature for 24 h, then treated with EtOAc (1.5 L) and water (1.5 L). The organic layer was separated, washed with water and brine, dried over sodium sulfate, filtered and evaporated. The oily residue was purified by column (0-35% EtOAc in hexane) to give {[3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-benzoyl]-methyl-amino}-acetic acid ethyl ester, 17 g (67%). LC-MS (ES) calculated for C26H25F2NO5, 469; found m/z 470 [M+H]+.

Provenance & Evidence