Hydrochloric Acid → HCID 58399165、化合物

HRID 475495

反応式

HRID 475495 の反応式
[H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][C:13]([O:15][CH3:16])=[O:14])=[CH:4]1.[Si]([O:24][CH2:25][CH2:26][C@@H:27]1[CH2:29][N:28]1[S:30]([C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=1)(=[O:32])=[O:31])(C(C)(C)C)(C)C.[CH3:40]I.Cl>CN(C=O)C.CCOC(C)=O.CC(OC)(C)C>[F:39][C:36]1[CH:37]=[CH:38][C:33]([S:30]([N:28]([CH3:40])[C@H:27]([CH2:26][CH2:25][OH:24])[CH2:29][N:3]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([CH2:12][C:13]([O:15][CH3:16])=[O:14])=[CH:4]2)(=[O:32])=[O:31])=[CH:34][CH:35]=1

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 74706Methyl indole-3-acetateHCID 58399169(2R)-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1-[(4-fluoro-phenyl)sulfonyl]aziridine

生成物 1

HCID 58399165HCID 58399165、化合物収率 75%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒3 回HCID 8857Ethyl Acetate溶媒2 回HCID 15413tert-Butyl methyl ether溶媒

反応条件

温度
0 °C

実験手順

A three necked round bottom flask fitted with a magnetic stir bar, nitrogen inlet, temperature probe and addition funnel was charged with sodium hydride (2 equiv.) and DMF. The mixture was cooled to 0° C., and a solution of methyl 1H-indol-3-ylacetate (2 equiv.) from Step 5 in DMF (1 M) was added dropwise. After the addition, the reaction was stirred for 15 min, upon which a DMF (0.5 M) solution of (2R)-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1-[(4-fluorophenyl)sulfonyl]aziridine (1 equiv.) from Step 4 was added dropwise. The reaction was allowed to stir 1.5 h. Methyl iodide (5 equiv.) was then added to the reaction and stirred an additional 1 h. Aqueous 2M HCl (7.2 equiv.) was then added carefully to the reaction followed by an equal volume of EtOAc and stirring continued for 2 h. The solution was diluted with EtOAc and layers separated. The organic phase was washed with ½ saturated brine (2×), dried over Na2SO4, filtered and concentrated to an orange syrup. The syrup was diluted with MTBE upon which solid started to form. The suspension was vigorously stirred while additional MTBE was added dropwise over 15 min. The suspension was cooled to 0° C. and Heptanes was added dropwise. The reaction was stirred for 1 h, and filtered. The solid cake was washed with MTBE/Heptanes (2:1) and dried on the fit under nitrogen for 16 h to provide the title compound (75%) as a white solid.

後処理

  1. customA three necked round bottom flask fitted with a magnetic stir bar, nitrogen inlet
  2. additiontemperature probe and addition funnel
  3. additionAfter the addition
  4. additionwas added dropwise
  5. stirringstirred an additional 1 h
  6. stirringstirring
  7. waitcontinued for 2 h
  8. customseparated
  9. washThe organic phase was washed with ½ saturated brine (2×)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated to an orange syrup
  13. additionThe syrup was diluted with MTBE upon which solid
  14. customto form
  15. additionwas added dropwise over 15 min
  16. temperatureThe suspension was cooled to 0° C.
  17. stirringThe reaction was stirred for 1 h
  18. filtrationfiltered
  19. washThe solid cake was washed with MTBE/Heptanes (2:1)
  20. customdried on the fit under nitrogen for 16 h

出典と根拠

ORDレコード
ord-a4b8fcf8680549b19254db087c0abb13
出典データセット
uspto-grants-2014_01
特許番号
US08637541B2

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