Sodium triacetoxyborohydride → 1,1-dimethylethyl {(3S,4R)-1-[2-(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl]-3-hydroxy-4-piperidinyl}carbamate

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Reaction Steps

(7-Fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)acetaldehyde methyl hemiacetal (200 mg, 0.8396 mmol) and 1,1-dimethylethyl[(3S,4R)-3-hydroxy-4-piperidinyl]carbamate (for a synthesis see WO2004058144, Example 5(c), cis-(3-hydroxy-piperidin-4-yl)-carbamic acid tert-butyl ester Enantiomer 2) (192 mg, 1 eq.) were stirred in chloroform (10 ml) plus MeOH (0.5 ml) under argon for 2 h. Sodium triacetoxyborohydride (534 mg, 3 eq.) was added in one portion and the mixture was stirred at rt over the weekend, then quenched by addition of saturated aqueous sodium hydrogen cabonate (2 mL). The organic phase was separated using a hydrophobic frit and the aqueous phase was extracted with DCM (2×20 ml). The organic extracts were combined, dried over anhydrous magnesium sulphate, filtered and evaporated under reduced pressure to give the crude product, which was purified by column chromatography on silica, eluted with 0-20% (2M ammonia in MeOH) in DCM. Appropriate fractions were combined and evaporated under reduced pressure to give 1,1-dimethylethyl {(3S,4R)-1-[2-(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl]-3-hydroxy-4-piperidinyl}carbamate (310 mg) as a tan foam.

Provenance & Evidence