Sodium hydride → 4-((2,3-Dimethyl-4-nitrophenoxy)methyl)pyridin-2-amine

HRID 571103

反応式

HRID 571103 の反応式
[NH2:1][C:2]1[CH:7]=[C:6]([CH2:8][OH:9])[CH:5]=[CH:4][N:3]=1.[H-].[Na+].F[C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[C:15]([CH3:22])[C:14]=1[CH3:23]>CN(C=O)C.[NH4+].[Cl-].C(#N)C>[CH3:23][C:14]1[C:15]([CH3:22])=[C:16]([N+:19]([O-:21])=[O:20])[CH:17]=[CH:18][C:13]=1[O:9][CH2:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH2:1])[CH:7]=1

参加物

7

反応物 3

HCID 24758Sodium hydrideHCID 1515296(2-Aminopyridin-4-yl)methanolHCID 247212012,3-Dimethyl-4-fluoronitrobenzene

生成物 1

HCID 674497664-((2,3-Dimethyl-4-nitrophenoxy)methyl)pyridin-2-amine

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒2 回HCID 6342Acetonitrile溶媒HCID 25517Ammonium Chloride溶媒

反応条件

温度
0 °C

実験手順

To a stirred solution of (2-aminopyridin-4-yl)methanol (1.33 g, 10.8 mmol) in DMF (10 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil, 537 mg, 13.4 mmol) and the reaction mixture maintained at 0° C. for 5 min and then warmed to RT for 1 hr. The mixture was re-cooled to 0° C., treated with a solution of 1-fluoro-2,3-dimethyl-4-nitrobenzene (2.00 g, 12.0 mmol) in DMF (5.0 mL) and after 2 min was warmed to RT. After 20 hr the reaction mixture was diluted with saturated aq. NH4Cl (50 mL) and extracted with EtOAc (2×100 mL) and then ether (100 mL). The combined organic extracts were dried and evaporated in vacuo to afford a red oil. The residue was diluted with acetonitrile (50 mL), upon which a brown precipitate formed. The precipitate was removed by filtration and the filtrate was evaporated in vacuo. This residue was purified by flash column chromatography (SiO2, 80 g, MeOH in DCM, 0-5%, gradient elution) to afford the title compound, Intermediate C3, as a yellow solid (1.19 g, 39%); Rt 1.35 (Method 2); m/z 274 (M+H)+ (ES+).

後処理

  1. temperaturewarmed to RT for 1 hr
  2. temperatureThe mixture was re-cooled to 0° C.
  3. temperaturewas warmed to RT
  4. extractionextracted with EtOAc (2×100 mL)
  5. customThe combined organic extracts were dried
  6. customevaporated in vacuo
  7. customto afford a red oil
  8. customformed
  9. customThe precipitate was removed by filtration
  10. customthe filtrate was evaporated in vacuo
  11. customThis residue was purified by flash column chromatography (SiO2, 80 g, MeOH in DCM, 0-5%, gradient elution)

出典と根拠

ORDレコード
ord-847a91f49fb940938347ef84d821417a
出典データセット
uspto-grants-2015_05
特許番号
US09024041B2

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