A solution of 1,1-dimethylethyl (1-{(2R)-2-hydroxy-3-[7-(methyloxy)-2-oxo-3,4-dihydro-1,8-naphthyridin-1(2H)-yl]propyl}-4-piperidinyl)carbamate (3.9 g, 8.97 mmol) in chloroform (150 ml) and triethylamine (3.1 ml) under argon was treated with methanesulfonic anhydride (3.1 g, 17.94 mmol) at room temperature and then heated at reflux for 2.5 h. The solvents were evaporated and the residue dissolved in acetonitrile (150 ml) and treated with sodium iodide (6.7 g, 44.85 mmol) and heated at 80° C. After 45 minutes acetonitrile was evaporated and the residue was partitioned between water (250 ml) and 20% methanol/dichloromethane (250 ml); the layers were separated and the aqueous layer was extracted with 20% methanol/dichloromethane (4×250 ml). The combined organic extracts were dried on magnesium sulphate, filtered and evaporated. The crude was purified by silica chromatography using a 0-10% methanol/dichloromethane gradient to provide the desired compound as a bright orange foam (1.83 g; 57%, impure with triethylamine residues). The aqueous layer was evaporated and then treated with chloroform; the solid was filtered off and the chloroform was evaporated to give 2.77 g of a yellow solid. The solid was dissolved in methanol and loaded onto a SCX cartridge which was pre-wet with methanol. The cartridge was washed with methanol (50 ml) and then with 2M ammonia in methanol (50 ml). The 2M ammonia in methanol was evaporated to afford the pure product as a white solid (220 mg), presumed 2:1 mixture of R:S).
