Sodium hydride → Tert-butyl(r)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperidine-1-carboxylate

HRID 856222노트

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HRID 856222 반응식
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:24]1[N:25]([CH2:32][C@:33]2([CH3:36])[CH2:35][O:34]2)[CH:26]=[C:27]([N+:29]([O-:31])=[O:30])[N:28]=1>CN(C=O)C>[CH3:35][C@@:33]1([CH2:36][O:1][C:2]2[CH:7]=[CH:6][C:5]([CH:8]3[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:12][CH2:13]3)=[CH:4][CH:3]=2)[O:34][C:24]2=[N:28][C:27]([N+:29]([O-:31])=[O:30])=[CH:26][N:25]2[CH2:32]1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 10443353(R)-2-chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazoleHCID 19381871tert-Butyl 4-(4-hydroxyphenyl)piperidine-1-carboxylate

생성물 1

HCID 67275180Tert-butyl(r)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperidine-1-carboxylate수율 48.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
80 °C

실험 절차

Tert-butyl 4-(4-hydroxyphenyl)piperidine-1-carboxylate (1.07 g, 3.86 mmol) was dissolved in DMF (10 ml). To the solution, sodium hydride (185 mg, 4.63 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 (923 mg, 4.24 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 solution 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/methanol=200/1) and then crystallized from ethyl acetate-diisopropyl ether to afford tert-butyl (R)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperidine-1-carboxylate (857 mg, yield 48%) as a white powder.

후처리

  1. temperaturewith cooling on ice-bath
  2. stirringthe solution was stirred for further 20 minutes at 80° C
  3. stirringthe solution 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/methanol=200/1)
  12. customcrystallized from ethyl acetate-diisopropyl ether

출처 및 근거

ORD 기록
ord-057a95783da4436c8a1efb4f7757e80b
출처 데이터셋
uspto-grants-2007_08
특허 번호
US07262212B2

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