[F:1][C:2]([F:18])([F:17])[C:3]([NH:5][C@@H:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9](=[O:16])[CH2:8][CH2:7]1)=[O:4].C(O)=O>CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]([F:17])([F:18])[C:3]([NH:5][C@@H:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C@H:9]([OH:16])[CH2:8][CH2:7]1)=[O:4]A solution of Intermediate 1b (161 g, 624 mmol) in DMF (2 L) was vacuum degassed with argon. [N-[(1R,2R)-2-(Amino-κN)-1,2-diphenylethyl]-4-methylbenzenesulfonamidato-κN]chloro[(1,2,3,4,5,6-η)-1-methyl-4-(1-methylethyl)benzene]-ruthenium (CAS: 192139-92-7, 9.95 g, 15.6 mmol) was then added. Formic acid (57.5 g, 1.25 mol) was added slowly to ice cold triethylamine (126 g, 1.25 mol) with stirring, this was then added to the DMF solution. The resulting reaction mixture was heated to 50° C. (internal temperature) for 41 h with stirring. LCMS analysis of the reaction indicated it was incomplete, therefore a solution of formic acid (14.4 g, 313 mmol) was added slowly to ice cold triethylamine (31.6 g, 312 mmol), this was then added to the reaction mixture. Heating was continued for an additional 22 h. After cooling, the mixture was concentrated in vacuo to give an orange residue. The residue was diluted with ethyl acetate (1.5 L) and the solution washed with brine (2×0.5 L). The organics were dried (Na2SO4), filtered and concentrated in vacuo. Purification by column chromatography (Silica, 3 Kg, 0-50% ethyl acetate in cyclohexane) gave Intermediate 1c (118 g, 73%). 97.5 d.e.% determination by LCMS Rt 3.37 min, M-H 258 (93.7%, desired); Rt 3.25 min, M-H 258 (1.2%, trans isomer). 1H NMR (400 MHz, CDCl3): 1.88-1.92 (1H, d, J=4.8 Hz), 1.98-2.18 (4H, m), 4.80-4.88 (1H, m), 5.165-5.24 (1H, m), 6.70-6.80 (1H, br s), 7.25-7.30 (1H, m), 7.30-7.40 (2H, m), 7.45-7.50 (1H, m).
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