H-D-CHG-OH HCL

Method 49; (2R)-cycloheXyl [(N-{[4-((2R, 3R)-1-(4-fluorophenyl)-3-f [2-(4-fluorophenyl)-2- oxoethyl] thio}-4-oxoazetidin-2-yl) phenoxy] acetyl} glycyl) amino] acetic acid; TBTU (0. 0092 g, 0.029 mmol) was added to a mixture of 3- (R)-4- (R)-1- (4-Fluorophenyl)-3- [(4-fluorobenzoyl) methylthio]-4-{4-[N-(carboxymethyl) carbamoylmethoxy] phenyl} azetidin- 2-one (0.016g, 0.030 mmol) and N-methylmorpholin (0.101 ml, 0. 98 mmol) in DMF (2ml). The mixture was stirred overnight under N2-atmosphere. Additional TBTU (0.0092 g, 0.029 mmol) was added and the mixture was stirred at 35°C for 2 h. (2R)-amino (cyclohexyl) acetic acid hydrochloride (0.0068 g, 0.035 mmol) was added. The mixture was stirred at 35°C for 2 h and at room temperature overnight. The solvent was removed under reduced pressure and the residue was purified by preparative HPLC on a Kromasil C8-column using a gradient of 5-100percent MeCN in 0.15percent trifluoroacetic acid buffer as eluent. The solvent was removed under reduced pressure and 0.009 g (47 percent) of the title product was obtained. M/z 680.01Example A: (R)-amino-cyclohexyl-acetic acid methyl ester hydrochloride