Methyl iodide → (S)-Benzyl 3-((tert-butoxycarbonyl)(methyl)amino)pyrrolidine-1-carboxylate

HRID 338854ノート

反応式

HRID 338854 の反応式
[H-].[Na+].[C:3]([O:7][C:8]([NH:10][C@H:11]1[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH2:12]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].I[CH3:27]>CN(C=O)C.O>[C:3]([O:7][C:8]([N:10]([CH3:27])[C@H:11]1[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH2:12]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

参加物

6

反応物 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 14555479Benzyl (3S)-3-[(tert-butoxycarbonyl)amino]pyrrolidine-1-carboxylate

生成物 1

HCID 59402251(S)-Benzyl 3-((tert-butoxycarbonyl)(methyl)amino)pyrrolidine-1-carboxylate収率 69%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
0 °C

実験手順

To a suspension of 60% dispersion of sodium hydride in mineral oil (1.5 g, 37.5 mmol) in anhydrous DMF (20 mL) cooled on an ice-bath to 0° C. was added dropwise a solution of (S)-benzyl 3-(tert-butoxycarbonylamino)pyrrolidine-1-carboxylate (10 g, 31.2 mmol) in anhydrous DMF (100 mL). The resulting mixture was stirred at 0° C. for 1 hour then at ambient temperature for 2 hours. The mixture was subsequently cooled to 0° C. and treated dropwise with iodomethane (2.1 mL, 34.3 mmol), and the mixture stirred at 0° C. for 1 hour then warmed to ambient temperature and stirred for 18 hours. The reaction mixture was diluted with water (300 mL) and the mixture extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residual oil was purified by column chromatography (Biotage, 65M; 10-20% ethyl acetate:hexanes) to afford (S)-benzyl 3-(tert-butoxycarbonyl(methyl)amino)pyrrolidine-1-carboxylate (7.2 g, 69%).

後処理

  1. waitat ambient temperature for 2 hours
  2. temperatureThe mixture was subsequently cooled to 0° C.
  3. stirringthe mixture stirred at 0° C. for 1 hour
  4. temperaturethen warmed to ambient temperature
  5. stirringstirred for 18 hours
  6. extractionthe mixture extracted with ethyl acetate
  7. washThe combined organic layers were washed with water and brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residual oil was purified by column chromatography (Biotage, 65M; 10-20% ethyl acetate:hexanes)

出典と根拠

ORDレコード
ord-dd6c1e6c641a4a21afc0c2fbb14d4e0a
出典データセット
uspto-grants-2014_11
特許番号
US08889704B2

反応ノート

読み込み中…