Citric Acid → N-(5-bromo-2-ethoxypyridin-3-yl)methanesulfonamide

HRID 241053ノート

反応式

HRID 241053 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([NH2:11])[C:5]([O:8][CH2:9][CH3:10])=[N:6][CH:7]=1.C(N(C(C)C)CC)(C)C.[CH3:21][S:22](Cl)(=[O:24])=[O:23].[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl.O1CCOCC1.[OH-].[Na+].O>[Br:1][C:2]1[CH:3]=[C:4]([NH:11][S:22]([CH3:21])(=[O:24])=[O:23])[C:5]([O:8][CH2:9][CH3:10])=[N:6][CH:7]=1

参加物

10

反応物 5

HCID 311Citric AcidHCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 532116995-Bromo-2-ethoxypyridin-3-amine

生成物 1

HCID 66820654N-(5-bromo-2-ethoxypyridin-3-yl)methanesulfonamide収率 44%

試薬・触媒・溶媒 4

HCID 14798Sodium Hydroxide触媒HCID 962Water溶媒2 回HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

実験手順

A solution of 5-bromo-2-ethoxypyridin-3-amine (53 mg, 0.25 mmol) and diisopropylethylamine (96 uL, 0.55 mmol) in dichloromethane (1 mL) was cooled to 0° C. and methanesulfonyl chloride (39 uL, 0.5 mmol) was added. The mixture was allowed to warm to rt over 15 h, and then water was added. The resulting mixture was extracted with dichloromethane. The organic extract was dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was dissolved in methanol (500 uL) and dioxane (500 uL), and then sodium hydroxide (2 M, 190 uL, 0.38 mmol) was added. The mixture was heated to 60° C. and 3 drops of aqueous sodium hydroxide (50%) were added. After stirring a further 30 min, the mixture was cooled to rt. Dilution with water was followed by acidification with aqueous citric acid (10%) and then two extractions with ethyl acetate. The combined organic extracts were washed with water, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (gradient 100% hexanes to 70% hexanes:30% ethyl acetate) to provide N-(5-bromo-2-ethoxypyridin-3-yl)methanesulfonamide (32.1 mg, 0.11 mmol, 43% yield) as a colorless film. 1H NMR (400 MHz, CDCl3) δ 7.95 (d, 1H), 7.89 (d, 1H), 6.75 (br s, 1H), 4.42 (q, 2H), 3.05 (s, 3H), 1.41 (t, 3H); MS (EI) for C8H11BrN2O3S: 295, 297 (Br isotopes, MH+).

後処理

  1. extractionThe resulting mixture was extracted with dichloromethane
  2. extractionThe organic extract
  3. dry with materialwas dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in methanol (500 uL)
  7. temperatureThe mixture was heated to 60° C.
  8. temperaturethe mixture was cooled to rt
  9. extractiontwo extractions with ethyl acetate
  10. washThe combined organic extracts were washed with water
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by flash chromatography (gradient 100% hexanes to 70% hexanes:30% ethyl acetate)

出典と根拠

ORDレコード
ord-c9f221847c7844a9989a7b271be2c4fb
出典データセット
uspto-grants-2014_02
特許番号
US08648066B2

反応ノート

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