Diisopropylethylamine → N1-butyl-N3-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R)-4-hydroxy-4-phenylpyrrolidin-2-yl)propan-2-yl)-N1-methylisophthalamide

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Step 6 (C): Preparation of (2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-2-(3-(carbamoyl)benzamido)-3-(3,5-difluorophenyl)propyl)-4-hydroxypyrrolidine-1-carboxylate. To a solution of 3-(butyl(methyl)carbamoyl)benzoic acid (Preparation F, 146 mg, 0.62 mmol) in dichloromethane (8 mL) was added Hunig's base (182 mg, 1.41 mmol) to make a clear solution and HATU (250 mg, 0.66 mmol) was then added. After stirring for 30 min, the reaction mixture was added (2R,4R)-tert-butyl 2-((1S,2S)-2-amino-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)-4-hydroxypyrrolidine-1-carboxylate (Step 6 (B), 230 mg, 0.47 mmol) and the reaction mixture was stirred at rt for 3 h. The crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% to 60% EtOAc/Hexane step gradient) to give 350 mg of the title compound: 1H NMR (CDCl3, 500 MHz) δ 0.01-0.07 (6H, m), 0.66 (2H, m), 0.83 (9H, s), 1.02 (1H, m), 1.30 (1H, m), 1.38 (9H, s), 1.53 (1H, m), 2.10 (2H, s), 2.60 (1H, m), 2.70 (1H, m), 2.79 (2H, s), 2.89-2.94 (2H, m), 3.09-3.16 (3H, m), 3.43 (1H, brd s), 3.56 (1H, dd, J=5, 10 Hz), 3.97-4.02 (2H, m), 4.16 (1H, brd s), 4.31-4.38 (2H, m), 6.48 (1H, m), 6.65-6.71 (2H, m), 7.25-7.34 (2H, m), 7.56-7.63 (2H, m), 7.83 (1H, s). MS (ESI) (M+H)+ 704.43.

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