Sodium hydride → 2-Benzyloxycarbonylamino-2-methyl-N-[2,3,4,5-tetra-hydro-4-oxo-1-[[2'-[(t-butoxycarbonylamino)methyl]-[1,1'-biphenyl]-4-yl]methyl]-1H-naphtho[2,1-b]azepin-3(R)-yl]-propanamide

Participants

Reaction Steps

To a solution of 2-benzyloxycarbonylamino-2-methyl-N-[2,3,4,5-tetrahydro-4-oxo-1H-naphtho[2,1-b]azepin-3(R)-yl]prop-anamide (Step A) in dry dimethylformamide under nitrogen at 0° C. is added of 60% sodium hydride/oil dispersion (1.05 eq.). After stirring for 15 minutes, a solution of 2′-[(t-butoxycarbonylamino)methyl]-1,1′-biphenyl-4-methanol, methanesulfonate ester (Step F) in dimethylformamide is added by cannula. The flask which originally contained the methanesulfonate ester is rinsed with dimethylformamide which is added to the reaction mixture. After stirring at 0° C. for 15 minutes, the reaction mixture is diluted with ethyl acetate and 50% saturated ammonium chloride. The mixture is transferred to a separatory funnel and the aqueous layer is separated. The organic layer is washed with 100 mL of saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride. The organic layer is dried over magnesium sulfate, filtered and the solvent removed under vacuum. The residue is purified by flash chromatography on silica gel eluting with ethyl acetate/hexane to afford the product.

Provenance & Evidence