Pyrazole → HCID 89853540、化合物

HRID 931072ノート

反応式

HRID 931072 の反応式
[H-].[Na+].[NH:3]1[CH:7]=[CH:6][CH:5]=[N:4]1.Br[C:9]1([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:12][CH2:11][CH2:10]1.CN(P(N(C)C)(N(C)C)=O)C>CN(C)C=O.O1CCCC1>[N:3]1([C:9]2([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:12][CH2:11][CH2:10]2)[CH:7]=[CH:6][CH:5]=[N:4]1

参加物

7

反応物 4

HCID 1048PyrazoleHCID 12679HexamethylphosphoramideHCID 24758Sodium hydrideHCID 97595Ethyl 1-bromocyclobutanecarboxylate

生成物 1

HCID 89853540HCID 89853540、化合物収率 47.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 8028Tetrahydrofuran溶媒2 回

実験手順

Into a 50 mL round bottom flask was added sodium hydride (60% dispersion in mineral oil, 452 mg, 11 mmol) and anhydrous tetrahydrofuran (18 mL). To the mixture was added pyrazole (511.6 mg, 7.515 mmol) and anhydrous tetrahydrofuran (1 mL). The mixture was stirred at room temperature for 2 h and then cooled to 0° C. Ethyl 1-bromocyclobutanecarboxylate (1.3 mL, 7.5 mmol) was added dropwise. The reaction mixture was stirred at 0° C. for 45 minutes and at room temperature over three days. HMPA (1.35 mL, 7.5 mmol) was added and the mixture was stirred at room temperature for 2 h. The reaction mixture was warmed to 70° C. for 2 h followed by the addition of N,N-dimethylformamide (4 mL). The reaction mixture was stirred at 70° C. for another 2 h before more N,N-dimethylformamide (2 mL) was added and then stirred at 70° C. for 18 h. The solvent was removed under reduced pressure. To the residue was added water and extracted with a mixture of heptanes and ethyl acetate (3×). The combined organics were dried over magnesium sulfate, filtered and concentrated under reduced pressure. Flash chromatography (0-40% ethyl acetate in heptanes) provided impure ethyl 1-(1H-pyrazol-1-yl)cyclobutanecarboxylate (688 mg), which was used without further purification.

後処理

  1. temperaturecooled to 0° C
  2. stirringThe reaction mixture was stirred at 0° C. for 45 minutes and at room temperature over three days
  3. stirringthe mixture was stirred at room temperature for 2 h
  4. temperatureThe reaction mixture was warmed to 70° C. for 2 h
  5. additionwas added
  6. stirringstirred at 70° C. for 18 h
  7. customThe solvent was removed under reduced pressure
  8. additionTo the residue was added water
  9. extractionextracted with a mixture of heptanes and ethyl acetate (3×)
  10. dry with materialThe combined organics were dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-ce4ee1ab03264825b1b522be603d0b71
出典データセット
uspto-grants-2016_03
特許番号
US09296745B2

反応ノート

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