Methanesulfonyl chloride → tert-Butyl 4-cyano-3,6-dihydropyridine-1(2H)-carboxylate

HRID 1053961ノート

反応式

HRID 1053961 の反応式
CS(Cl)(=O)=O.[C:6]([C:8]1(O)[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1)#[N:7].C(N(C(C)C)C(C)C)C>C(Cl)(Cl)Cl>[C:6]([C:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH:9]=1)#[N:7]

参加物

5

反応物 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 533992621-Boc-4-cyano-4-hydroxypiperidine

生成物 1

HCID 68431027tert-Butyl 4-cyano-3,6-dihydropyridine-1(2H)-carboxylate

試薬・触媒・溶媒 1

HCID 6212Chloroform溶媒

反応条件

温度
0 °C

実験手順

Methanesulfonyl chloride (0.189 mL, 2.43 mmol) was added to a mixture of tert-butyl 4-cyano-4-hydroxypiperidine-1-carboxylate (500 mg, 2.21 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.579 mL, 3.31 mmol) in chloroform (8.8 mL) at 0° C. The reaction mixture was stirred at 0° C. for 45 minutes, and was then partitioned between dichloromethane and water. The organic layer was dried over anhydrous sodium sulfate, and the dried solution was filtered. The filtrate was concentrated in vacuo, and the residue was dissolved in pyridine (5.5 mL). The reaction mixture was heated to 120° C. for 4 hours, and was then cooled to ambient temperature. The cooled reaction mixture was partitioned between ethyl acetate and water, and the organic layer was washed sequentially with water and saturated aqueous sodium chloride solution. The washed solution was dried over anhydrous sodium sulfate, and the dried solution was filtered. The filtrate was concentrated in vacuo, and the residue was purified by flash-column chromatography (using a gradient elution of 0-100%, ethyl acetate/hexanes) to afford the title compound. 1H NMR (500 MHz, CDCl3): δ 6.55 (br s, 1H), 4.05 (m, 2H), 3.55 (t, J=5.6 Hz, 2H), 2.34 (br s, 2H), 1.46 (s, 9H).

後処理

  1. customwas then partitioned between dichloromethane and water
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationthe dried solution was filtered
  4. concentrationThe filtrate was concentrated in vacuo
  5. dissolutionthe residue was dissolved in pyridine (5.5 mL)
  6. temperatureThe reaction mixture was heated to 120° C. for 4 hours
  7. temperaturewas then cooled to ambient temperature
  8. customThe cooled reaction mixture
  9. customwas partitioned between ethyl acetate and water
  10. washthe organic layer was washed sequentially with water and saturated aqueous sodium chloride solution
  11. dry with materialThe washed solution was dried over anhydrous sodium sulfate
  12. filtrationthe dried solution was filtered
  13. concentrationThe filtrate was concentrated in vacuo
  14. customthe residue was purified by flash-column chromatography (
  15. washa gradient elution of 0-100%, ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-111ec17b6a394e53a81c574a8eeccd0d
出典データセット
uspto-grants-2016_07
特許番号
US09394282B2

反応ノート

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