To a solution of the compound 22 (100 g, 344 mmol), benzyl alcohol (46 ml, 447 mmol), and tributylphosphine (128 ml, 516 mmol) in tetrahydrofuran (1000 ml) was added a 40% diisopropyl azodicarboxylate-toluene solution (280 ml, 516 mmol) under ice-cooling over 30 minutes. After stirred for 30 minutes under ice-cooling, a temperature was raised to room temperature, followed by stirring for 2 hours. The solvent was distilled off under reduced pressure, to the residue were added toluene (100 ml) and hexane (2000 ml), and precipitated crystals were filtered. The solvent was distilled off under reduced pressure, to the residue were added diethyl ether (200 ml) and hexane (2000 ml), and precipitated crystals were filtered. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate). 4-Benzyloxy-N-(4-fluorobenzyl)-5-methoxy-6-methylnicotinamide 23 (68.5 g, 52%) was obtained as a colorless crystal.
