Water → tert-butyl 2-(2-(2H-1,2,3-triazol-2-yl)benzyl)-1-oxo-2,9-diazaspiro[5.5]-undecane-9-carboxylate

HRID 41576

反応式

HRID 41576 の反応式
[H-].[Na+].[O:3]=[C:4]1[C:9]2([CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[CH2:8][CH2:7][CH2:6][NH:5]1.Br[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[N:30]1[N:34]=[CH:33][CH:32]=[N:31]1.O>CCCC[N+](CCCC)(CCCC)CCCC.[I-].C1COCC1>[N:31]1[N:30]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[CH2:23][N:5]2[CH2:6][CH2:7][CH2:8][C:9]3([CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH2:14]3)[C:4]2=[O:3])[N:34]=[CH:33][CH:32]=1

参加物

7

反応物 4

HCID 962WaterHCID 24758Sodium hydrideHCID 49760149tert-Butyl 1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylateHCID 672510032-(2-(Bromomethyl)phenyl)-2H-1,2,3-triazole

生成物 1

HCID 67253417tert-butyl 2-(2-(2H-1,2,3-triazol-2-yl)benzyl)-1-oxo-2,9-diazaspiro[5.5]-undecane-9-carboxylate収率 99%

試薬・触媒・溶媒 2

HCID 67553Tetrabutylammonium Iodide触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

NaH (308 mg, 7.69 mmol, 60% in mineral oil) was added to an ice-cold solution of tert-butyl 1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate [1198284-94-4] (1.127 g, 4.08 mmol), 2-(2-(bromomethyl)phenyl)-2H-1,2,3-triazole (described separately as building block) (1.0 g, 4.16 mmol) and TBAI (78 mg, 0.208 mmol) in THF (30 mL). The resulting mixture was stirred at 0° C. for 1 h. The reaction mixture was allowed to warm to rt and stirred for 4 h. To the mixture water was added and the solution was extracted twice with ethyl acetate. The organic layer was washed with water and brine, filtered and dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure. The product was purified by flash-column chromatography over silicagel (eluent: gradient 5%-65% ethyl acetate/heptane) to yield the title compound (1.77 g, 99%). [1H NMR (400 MHz, DMSO-d6) ♀ ppm 8.11 (s, 2H), 7.61-7.59 (m, 1H), 7.52-7.46 (m, 2H), 7.23 (d, 1H), 4.53 (s, 2H), 3.69-3.65 (m, 2H), 3.11-3.07 (m, 2H), 3.03 (br s, 2H), 1.86-1.72 (m, 6H), 1.45-1.40 (m, 2H), 1.38 (s, 9H); LCMS RtA=1.17, [M+H]+=426.4].

後処理

  1. temperatureto warm to rt
  2. stirringstirred for 4 h
  3. extractionthe solution was extracted twice with ethyl acetate
  4. washThe organic layer was washed with water and brine
  5. filtrationfiltered
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationThe organic layer was concentrated under reduced pressure
  8. customThe product was purified by flash-column chromatography over silicagel (eluent: gradient 5%-65% ethyl acetate/heptane)

出典と根拠

ORDレコード
ord-7b1732bf507941bd853b395614f88582
出典データセット
uspto-grants-2013_09
特許番号
US08530648B2

関連ノート

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