A solution of 3-((4-(2-methylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)benzaldehyde (example 96, step a) (0.303 g), (R)-5-(2-amino-1-(tert-butyldimethylsilyloxy)ethyl)-8-hydroxyquinolin-2(1H)-one (WO2004106333) (0.330 g) and acetic acid (0.043 mL) in methanol (5 mL) was stirred at room temperature for 30 minutes, then cooled in an ice-water bath under nitrogen and treated with sodium triacetoxyborohydride (0.243 g) in one portion. The mixture was stirred in ice-water for 2 hours, then concentrated in vacuo. The residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution, the phases were separated, and the aqueous phase was extracted twice more with ethyl acetate. Any insoluble gummy residues were dissolved in methanol. The combined ethyl acetate phases were washed with brine, dried over magnesium sulphate and combined with the methanol solution. The whole was purified by flash chromatography on silica eluted with 1:7:92 triethylamine:methanol:dichloromethane to afford the slightly impure subtitled product as a yellow foam. Yield 0.324 g.
