Water → 4-Iodo-6-[3,5-bis(trifluoromethyl)benzyl]-6,7,8,9-tetrahydro-5H-10-oxa-1,6-diazabenzocyclooctene-5-one

N-[3,5-Bis(trifluoromethyl)benzyl]-2-chloro-N-(3-hydroxypropyl)-4-iodonicotinamide (compound of Reference Example 2; 6.86 g) was dissolved in tetrahydrofuran (60 mL). While the resulting solution was chilled on an ice bath, sodium hydride (581 mg, 60% oil suspension) was added, and the mixture was stirred for 30 minutes. The temperature of the mixture was then allowed to rise to room temperature, and the mixture was further stirred for 1 hour. While the reaction mixture was chilled on an ice bath, water was added, and then the resulting mixture was subjected to extraction with ethyl acetate. The resulting extract was washed with a saturated aqueous solution of sodium chloride, and was then dried on anhydrous sodium sulfate. The solvent was removed by distillation to obtain a residue, and then the residue was purified on a silica gel column chromatography (ethyl acetate:n-hexane=2:1) to obtain 5-[3,5-bis(trifluoromethyl)benzyl]-7-iodo6-oxo-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocine (2.69 g, 42%).