Hydrochloric Acid → 2-(1-Methyl-1H-indol-3-yl)acetamide

HRID 368735

反応式

HRID 368735 の反応式
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](CC#N)=[CH:2]1.[H-].[Na+].CI.Cl.[OH:18]O.[OH-].[Na+].[CH3:22][N:23]([CH:25]=O)[CH3:24]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl.O.CCOC(C)=O>[CH3:24][N:23]1[C:22]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([CH2:3][C:2]([NH2:1])=[O:18])=[CH:25]1

参加物

12

反応物 7

HCID 313Hydrochloric Acid2 回HCID 784Hydrogen PeroxideHCID 6228Dimethylformamide3 回HCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 351795Indole-3-acetonitrile

生成物 1

HCID 153579072-(1-Methyl-1H-indol-3-yl)acetamide収率 70%

試薬・触媒・溶媒 4

HCID 74236Tetrabutylammonium Bromide触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

A solution of indole-3-acetonitrile (10.0 g, 64.0 mmol) in DMF (50 mL) was added dropwise to a suspension of sodium hydride (3.33 g, 83.3 mmol) in DMF (20 mL) at room temperature. The resultant mixture was stirred for 30 minutes and was cooled to 0°-5° C., and a solution of methyl iodide (13.63 g, 96.0 mmol) in DMF (30 mL) was added dropwise. The reaction was allowed to warm and stir at room temperature for 3 hrs. The reaction was worked up extractively using EtOAc (300 mL) and aqueous 0.5 N HCl (400 mL) and the organic layer dried (MgSO4) and solvent removed in vacuo to give 16.34 g (>100%) of crude alkylated product that was carried on without purification as follows. The oil was combined with tetrabutylammonium bromide (4.13 g, 12.8 mmol) in CH2Cl2 (100 mL) and was cooled in an ice bath before a 30% aqueous solution of hydrogen peroxide (33 mL) was added followed by an aqueous 20% weight solution of NaOH (26 mL). The reaction was allowed to warm to room temperature and stir for 21 hours before being worked up extractively with CH2Cl2 (650 mL), aqueous 1N HCl (500 mL) and water (500 mL). The organic layer was dried (MgSO4) and solvent removed in vacuo to give a thick slurry to which was added hexanes (100 mL). This mixture was filtered using 1:1 CH2Cl2 : hexanes (100 mL) as a rinse to give 8.45 g (70%) of the titled product after drying. NMR. MS (FD) m/z=188 (M+, 100%). Anal. calc'd for C11H12N2O C, 70.19; H, 6.43; N, 14.88. Found C, 70.02; H, 6.17; N, 14.99.

後処理

  1. temperaturewas cooled to 0°-5° C.
  2. temperatureto warm
  3. dry with materialthe organic layer dried (MgSO4) and solvent
  4. customremoved in vacuo
  5. customto give 16.34 g (>100%) of crude alkylated product that
  6. customwas carried on without purification
  7. additionwas added
  8. temperatureto warm to room temperature
  9. stirringstir for 21 hours
  10. dry with materialThe organic layer was dried (MgSO4) and solvent
  11. customremoved in vacuo
  12. customto give a thick slurry to which
  13. filtrationThis mixture was filtered
  14. washhexanes (100 mL) as a rinse

出典と根拠

ORDレコード
ord-24062478ebcb4ee09cd87376cb487d90
出典データセット
uspto-grants-2000_10
特許番号
US06133452

関連ノート

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