To a solution of diphosgene (41 μL, 0.34 mmol) in 1:1 v/v toluene/tetrahydrofuran (18 mL total) at −35° C. under an atmosphere of dry argon was added a solution of (S)-2-{(R)-2-amino-2-[4-(2-tert-butoxy-ethoxy)-phenyl]-acetylamino}4,4-dimethyl-pentanoic acid (2-fluoro-4-iodo-phenyl)-amide (300 mg, 0.49 mmol) and N,N-diisopropylethylamine (260 μL, 1.47 mmol) in tetrahydrofuran (9 mL) dropwise with stirring over 10 minutes. After an additional 45 minutes ice was added and the reaction mixture stirred vigorously and warmed to ambient temperature. The reaction mixture was poured into water, extracted with ethyl acetate (twice) and the combined organic layers washed sequentially with water (twice), 0.1 M aqueous hydrochloric acid, water, saturated aqueous sodium hydrogen carbonate, water and brine, then dried over sodium sulfate, filtered and concentrated in vacuo to give (S)-2-{(R)-4-[4-(2-tert-butoxyethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}4,4-dimethylpentanoic acid (2-fluoro-4-iodo-phenyl)-amide as yellow sticky solid (295 mg, 95%) which was used in the subsequent step without further purification.
