In a 20 ml, pear-shaped flask, (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (416 mg, 2.38 mmol) and HATU (695 mg, 1.83 mmol) were combined with DMF (10 ml) to give a colorless solution. (S)-5-(4-bromophenyl)-2-(4,4-difluoropyrrolidin-2-yl)-1H-imidazole (600 mg, 1.83 mmol) in 2 ml of DMF was added and followed by drop wise addition of DIPEA (1.18 g, 1.6 ml, 9.14 mmol). It was stirred at room temperature for 1 hr then poured into ice/water. It was extracted with EtOAc (2×30 ml), washed with brine and water. The organic layer was dried over MgSO4, concentrated and purified on a silica gel column (CH2Cl2, 1%, 2%, 5% MeOH/CH2Cl2) to afford methyl (S)-1-((S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)-4,4-difluoropyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl-carbamate as an orange foaming solid. (650 mg, 73%): ESI-LRMS m/e calcd for C20H25BrF2N4O3 [M+] 485. found 486 [M+H+].
