To a solution of 5.0 g of tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(piperidin-4-yl)carbamate monohydrate in 40 mL of N-methyl-2-pyrrolidone, 3.5 g of (7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)acetaldehyde hydrochloride monohydrate was added, and the mixture was stirred for 1 hour at room temperature. To the mixture, 4.3 g of sodium triacetoxyborohydride was added dividedly in 5 portions over the period of 80 minutes under ice cooling, and the mixture was stirred for 1 hour and 40 minutes under ice cooling. After heating to room temperature, the mixture was added with 20 mL of water and adjusted to pH 11.5 with an aqueous solution of 20% sodium hydroxide. To the mixture, 20 mL of N-methyl-2-pyrrolidone was added at 70 to 80° C., and the mixture was stirred for 2 hours and 30 minutes at the same temperature. The reaction mixture was cooled to room temperature and the solid product was obtained by filtration and washed with water to give 6.5 g of tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(1-(2-(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate as a light brown solid.
