Lithium Hydroxide → 4-((5-bromo-1-isopropyl-1H-pyrazol-4-yl)methyl)-1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid

HRID 880893ノート

反応式

HRID 880893 の反応式
[Br:1][C:2]1[N:6]([CH:7]([CH3:9])[CH3:8])[N:5]=[CH:4][C:3]=1[CH2:10][C:11]1([C:24]([O:26]CC)=[O:25])[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1.[OH-].[Li+]>CO>[Br:1][C:2]1[N:6]([CH:7]([CH3:8])[CH3:9])[N:5]=[CH:4][C:3]=1[CH2:10][C:11]1([C:24]([OH:26])=[O:25])[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH2:13][CH2:12]1

参加物

4

反応物 2

HCID 3939Lithium Hydroxide2 回HCID 674915091-tert-butyl 4-ethyl 4-((5-bromo-1-isopropyl-1H-pyrazol-4-yl)methyl)piperidine-1,4-dicarboxylate

生成物 1

HCID 674917184-((5-bromo-1-isopropyl-1H-pyrazol-4-yl)methyl)-1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid収率 74.3%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
80 °C

実験手順

To a solution of 1-tert-butyl 4-ethyl 4-((5-bromo-1-isopropyl-1H-pyrazol-4-yl)methyl)piperidine-1,4-dicarboxylate (14.5 g, 31.6 mmol) in methanol (50 mL) was added lithium hydroxide (1.52 g, 36.2 mmol) and the mixture was stirred at 80° C. for 18 hours. An additional portion of lithium hydroxide (2.55 g, 63.3 mmol) was added and the mixture was heated under vigorous reflux for 3 hours, cooled to room temperature, the solvent was removed in vacuo. The residue was washed with ethyl acetate, filtered, and the filtrate was saved. The solids were dissolved in 2 N aqueous sodium hydroxide (40 mL) and then acidified to pH 5 with 10% citric acid solution. The aqueous solution was extracted with ethyl acetate (3×40 mL), the organics were combined, dried over magnesium sulfate, filtered and then combined with the original filtrate. The solvent was removed from the filtrate under reduced pressure and the resulting residue was purified by flash column chromatography (ethyl acetate/heptanes) to afford 4-((5-bromo-1-isopropyl-1H-pyrazol-4-yl)methyl)-1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (10.1 g, 74%) as a colorless solid. +ESI (M+H) 429.9; 1H NMR (300 MHz, CDCl3, δ): 7.41 (s, 1H), 4.64 (m, 1H), 3.94 (m, 2H), 2.95 (m, 2H), 2.68 (m, 2H), 2.09 (m, 2H), 1.47 (m, 17H).

後処理

  1. temperaturethe mixture was heated
  2. temperatureunder vigorous reflux for 3 hours
  3. temperaturecooled to room temperature
  4. customthe solvent was removed in vacuo
  5. washThe residue was washed with ethyl acetate
  6. filtrationfiltered
  7. dissolutionThe solids were dissolved in 2 N aqueous sodium hydroxide (40 mL)
  8. extractionThe aqueous solution was extracted with ethyl acetate (3×40 mL)
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. customThe solvent was removed from the filtrate under reduced pressure
  12. customthe resulting residue was purified by flash column chromatography (ethyl acetate/heptanes)

出典と根拠

ORDレコード
ord-52ed260a7939473b9479a79409f0f9de
出典データセット
uspto-grants-2015_03
特許番号
US08993586B2

反応ノート

読み込み中…