Sodium hydride → Delamanid

Participants

Reaction Conditions

Reaction Steps

4-[4-(4-Trifluoromethoxyphenoxy)piperidin-1-yl]phenol (17.4 g, 49.0 mmol) was dissolved in DMF (150 ml). To the solution, sodium hydride (2.15 g, 53.8 mmol) was added at room temperature, and the solution was stirred for 20 minutes at 80° C. To the solution, (R)-2-chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazole prepared in Example 12 (14.9 g, 68.6 mmol) was added with cooling on ice-bath, and the solution was stirred for further 20 minutes at 80° C. To the reaction mixture, ice-water was added, and the mixture was stirred vigorously. The precipitates were filtered off, washed with water and dissolved in methylene chloride. The solution was washed with a saturated saline solution, dried over magnesium sulfate and then filtered. The resulting filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/ethyl acetate=10/1) and then crystallized from methylene chloride/ethyl acetate to afford (R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethoxyphenoxy)piperidin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole (14.3 g, yield 55%) as a light yellow powder.

Provenance & Evidence