Sodium hydride → Tert-butyl 4-(4-fluorophenyl)-2-((5-methylisoxazol-3-yl)methyl)-1-oxo-2,7-diazaspiro[4.5]decane-7-carboxylate

HRID 1036725ノート

反応式

HRID 1036725 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:12]3([CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]3)[C:11](=[O:25])[NH:10][CH2:9]2)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:29][C:30]1[CH:34]=[C:33]([CH3:35])[O:32][N:31]=1>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:12]3([CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:13]3)[C:11](=[O:25])[N:10]([CH2:29][C:30]3[CH:34]=[C:33]([CH3:35])[O:32][N:31]=3)[CH2:9]2)=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 27763043-(Bromomethyl)-5-methylisoxazoleHCID 71060587HCID 71060587、化合物

生成物 1

HCID 71060659Tert-butyl 4-(4-fluorophenyl)-2-((5-methylisoxazol-3-yl)methyl)-1-oxo-2,7-diazaspiro[4.5]decane-7-carboxylate

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
0 °C

実験手順

Tert-butyl 4-(4-fluorophenyl)-1-oxo-2,7-diazaspiro[4.5]decane-7-carboxylate (200 mg; 0.574 mmol) was solubilised in DMF (5 ml) and cooled to 0° C. 60% Sodium hydride dispersion in mineral oil (46 mg, 1.148 mmol) was added and the mixture stirred at 0° C. for 45 minutes. 3-(Bromomethyl)-5-methylisoxazole (101 mg; 0.574 mmol) was solubilised in DMF (0.7 ml) and added. The reaction was stirred at 0° C. for 30 minutes then warmed to RT for 3 hr. The mixture was quenched with water and extracted with EtOAc. The organics were combined and washed with brine and dried over magnesium sulphate, filtered and concentrated in vacuo. The resultant oil was purified by chromatography on silica eluting with 50-100% TBME in iso-hexane to yield tert-butyl 4-(4-fluorophenyl)-2-((5-methylisoxazol-3-yl)methyl)-1-oxo-2,7-diazaspiro[4.5]decane-7-carboxylate.

後処理

  1. additionadded
  2. stirringThe reaction was stirred at 0° C. for 30 minutes
  3. temperaturethen warmed to RT for 3 hr
  4. customThe mixture was quenched with water
  5. extractionextracted with EtOAc
  6. washwashed with brine
  7. dry with materialdried over magnesium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resultant oil was purified by chromatography on silica eluting with 50-100% TBME in iso-hexane

出典と根拠

ORDレコード
ord-66470c6e41dc4b119b11ab847393b700
出典データセット
uspto-grants-2013_10
特許番号
US08546416B2

反応ノート

読み込み中…