Sodium hydride → Delamanid

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.

1. temperaturewith cooling on ice-bath
2. stirringthe solution was stirred for further 20 minutes at 80° C
3. stirringthe mixture was stirred vigorously
4. filtrationThe precipitates were filtered off
5. washwashed with water
6. dissolutiondissolved in methylene chloride
7. washThe solution was washed with a saturated saline solution
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. concentrationThe resulting filtrate was concentrated under reduced pressure
11. customThe residue was purified by silica gel column chromatography (methylene chloride/ethyl acetate=10/1)
12. customcrystallized from methylene chloride/ethyl acetate

ORD-Eintrag

ord-a05bab9f4ed446bd96666548f61f0163

Quelldatensatz

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07262212B2