咪唑 → 3-(tert-Butyl-dimethyl-silanyloxymethyl)-5-trifluoromethyl-phenylamine

HRID 1971332

反应方程式

HRID 1971332 反应方程式
[NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)C(O)=O.[H-].[H-].[H-].[H-].[Li+].[Al+3].[F-].[Na+].N1C=CN=[CH:24]1.[CH3:28][C:29]([Si:32](Cl)(C)C)([CH3:31])[CH3:30].CCO[C:39]([CH3:41])=[O:40]>C1COCC1.C(Cl)Cl.O>[C:29]([SiH2:32][O:40][C:39]([CH3:41])([CH3:24])[C:4]1[CH:3]=[C:2]([NH2:1])[CH:10]=[C:9]([C:11]([F:14])([F:12])[F:13])[CH:8]=1)([CH3:31])([CH3:30])[CH3:28]

参与物

10

反应物 6

HCID 795咪唑HCID 5235氟化钠HCID 8857乙酸乙酯HCID 28928叔丁基二甲基氯硅烷HCID 6095563-氨基-5-三氟甲基苯甲酸HCID 21226445Aluminium lithium hydride

产物 1

HCID 1373297753-(tert-Butyl-dimethyl-silanyloxymethyl)-5-trifluoromethyl-phenylamine

试剂、催化剂与溶剂 3

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 6344二氯甲烷溶剂HCID 8028四氢呋喃溶剂2 次

反应条件

温度
0 °C

实验过程

To a solution of 3-Amino-5-trifluoromethyl-benzoic acid (2.0 g, 9.76 mmol) in THF (40 mL) at 0° C. is added LiAlH4 in THF (1 M, 39 mL). The mixture is warmed to reflux and stirred for 62 h. The mixture is then cooled to 0° C. and NaF (2.2 g) is added followed by H2O (3.8 mL). The slurry is stirred for 10 minutes and then allowed to warm to rt and stir an additional 40 min. The mixture is filtered and the solid is rinsed with EtOAc and MeOH. The filtrate is concentrated and the crude residue is mixed with imidazole (2.66 g, 39 mmol) and DCM (30 mL) at 0° C. TBSCl (3.5 g, 23.4 mmol) is added and the mixture is stirred at rt for 5 h. The reaction mixture is then diluted with EtOAc, washed with saturated aqueous NaHCO3, brine, and dried over Na2SO4. Concentration provides the title compound that is carried on to next step without further purification. MS (ESI) m/z 306.1 (M+1).

后处理

  1. temperatureThe mixture is warmed
  2. temperatureto reflux
  3. stirringThe slurry is stirred for 10 minutes
  4. temperatureto warm to rt
  5. stirringstir an additional 40 min
  6. filtrationThe mixture is filtered
  7. washthe solid is rinsed with EtOAc and MeOH
  8. concentrationThe filtrate is concentrated
  9. stirringthe mixture is stirred at rt for 5 h
  10. washwashed with saturated aqueous NaHCO3, brine
  11. dry with materialdried over Na2SO4
  12. concentrationConcentration

来源与证据

ORD记录
ord-ee6f3c0f3ee64dfabae90c662dedfeb7
来源数据集
uspto-grants-2013_04
专利号
US08431584B2

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