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

HRID 617428

반응식

HRID 617428 반응식
[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

참가 물질

12

반응물 7

HCID 313Hydrochloric Acid2회HCID 784Hydrogen PeroxideHCID 6228Dimethylformamide3회HCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 351795Indole-3-acetonitrile

생성물 1

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

시약·촉매·용매 4

HCID 74236Tetrabutylammonium Bromide촉매HCID 962Water용매HCID 6344Dichloromethane용매2회HCID 8857Ethyl Acetate용매

실험 절차

A solution of indole-3-acetonitrile (10.0 g, 64.0 mnol) 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 0.5N 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.

후처리

  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

출처 및 근거

ORD 기록
ord-4ce952e30f164279a9c8ee31a3afa21d
출처 데이터셋
uspto-grants-1999_09
특허 번호
US05948907

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