Hydrogen Peroxide → (S)-2-(4-bromophenyl)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)acetic acid

HRID 79494ノート

反応式

HRID 79494 の反応式
OO.O[Li].O.C([C@@H]1COC(=O)N1[C:19](=[O:42])[C@H:20]([C@H:28]1[N:32]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C:31]([CH3:41])([CH3:40])[CH2:30][CH2:29]1)[C:21]1[CH:26]=[CH:25][C:24]([Br:27])=[CH:23][CH:22]=1)C1C=CC=CC=1.[O-:43]S([O-])=O.[Na+].[Na+]>C1COCC1.O.C1COCC1>[Br:27][C:24]1[CH:25]=[CH:26][C:21]([C@@H:20]([C@@H:28]2[CH2:29][CH2:30][C:31]([CH3:40])([CH3:41])[N:32]2[C:33]([O:35][C:36]([CH3:38])([CH3:39])[CH3:37])=[O:34])[C:19]([OH:43])=[O:42])=[CH:22][CH:23]=1

参加物

7

反応物 4

HCID 784Hydrogen PeroxideHCID 24437Sodium SulfiteHCID 168937Lithium hydroxide, monohydrateHCID 68735397HCID 68735397、化合物

生成物 1

HCID 59564917(S)-2-(4-bromophenyl)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)acetic acid収率 87%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 21881883Oxolane--water (1/1)溶媒

実験手順

30% H2O2 (0.67 mL, 7.0 mmol) was added to a solution of LiOH—H2O (0.24 g, 5.60 mmol) in THF/water (2:1, 93 mL), and the solution was stirred at room temperature for 10 minutes. The solution was then cooled to 0° C. and treated with a solution of (S)-tert-butyl 5-((S)-2-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-(4-bromophenyl)-2-oxo ethyl)-2,2-dimethylpyrrolidine-1-carboxylate (1.60 g, 2.80 mmol) in THF (10 mL). The reaction was stirred at 0° C. for 2 hours and allowed to warm to room temperature and stirred overnight. The reaction was then cooled to 0° C. and treated with 1M Na2SO3 (10 mL) and stirred for 10 minutes. The reaction was then warmed to room temperature and stirred for 10 minutes. The reaction was next concentrated and extracted with EtOAc (2×20 mL). The aqueous layer was then acidified with 1N HCl to a pH of about 1 to about 2 and extracted with DCM (2×20 mL). The combined DCM fractions were dried over sodium sulfate, filtered, and concentrated to give (S)-2-(4-bromophenyl)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)acetic acid (1.01 g, 87% yield) as a solid. MS ESI (+) m/z 412 detected.

後処理

  1. temperatureThe solution was then cooled to 0° C.
  2. stirringThe reaction was stirred at 0° C. for 2 hours
  3. temperatureto warm to room temperature
  4. stirringstirred overnight
  5. temperatureThe reaction was then cooled to 0° C.
  6. stirringstirred for 10 minutes
  7. temperatureThe reaction was then warmed to room temperature
  8. stirringstirred for 10 minutes
  9. concentrationThe reaction was next concentrated
  10. extractionextracted with EtOAc (2×20 mL)
  11. extractionextracted with DCM (2×20 mL)
  12. dry with materialThe combined DCM fractions were dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated

出典と根拠

ORDレコード
ord-b91ee707f94a45e1b2c7c913e98b996d
出典データセット
uspto-grants-2014_09
特許番号
US08841304B2

反応ノート

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