Hydrogen Peroxide → (S)-2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acid

HRID 79502ノート

反応式

HRID 79502 の反応式
[OH2:1].[OH-].[Li+].C1[CH2:8][O:7]CC1.O.OO.C([C@@H]1COC(=O)N1C(=O)[C@H:26]([C@@H:34]1[CH2:38][CH2:37][CH2:36][N:35]1[C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=1)C1C=CC=CC=1>C1COCC1>[C:42]([O:41][C:39]([N:35]1[CH2:36][CH2:37][CH2:38][C@H:34]1[C@H:26]([C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=1)[C:8]([OH:7])=[O:1])=[O:40])([CH3:45])([CH3:43])[CH3:44]

参加物

6

反応物 4

HCID 784Hydrogen PeroxideHCID 168937Lithium hydroxide, monohydrateHCID 21881883Oxolane--water (1/1)HCID 66845408(S)-tert-butyl 2-((S)-2-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-(4-chlorophenyl)-2-oxoethyl)pyrrolidine-1-carboxylate

生成物 1

HCID 59564918(S)-2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acid収率 72%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

Lithium hydroxide hydrate (0.0471 g, 1.12 mmol) was added to a solution of THF/water (3:1, 19 mL) and stirred until dissolved. The mixture was cooled to 0° C. and treated with 30% hydrogen peroxide (0.231 mL, 2.24 mmol) and stirred for 10 minutes. A solution of (S)-tert-butyl 2-((S)-2-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-(4-chlorophenyl)-2-oxoethyl)pyrrolidine-1-carboxylate (0.280 g, 0.561 mmol) in THF (2 mL) was added. The reaction was stirred for 30 minutes at 0° C. Thin layer chromatography (“TLC”) did not show much progress, therefore the reaction was allowed to warm to ambient temperature and stirred overnight. The reaction was quenched by addition of 1.5 M Na2SO3 (1 mL) and stirred for 15 minutes. The reaction mixture was diluted with Et2O and separated. The aqueous portion was washed (2×) with Et2O then adjusted to a pH of 1 with 3N HCl. The aqueous portion was extracted (3×) with ethyl acetate. The combined organic layers were washed with water (2×), saturated NaCl, dried over Na2SO4 and concentrated in vacuo to a thick oil which slowly solidified to give (S)-2-((S)-1-(tert-butoxycarbonyl)-pyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acid as a foam (0.55 g, 72%). 1H NMR (CDCl3, 400 MHz) □7.30 (d, 2H), 7.21 (d, 2H), 4.53-4.40 (m, 1H), 4.37-4.27 (m, 1H), 3.34-3.22 (m, 1H), 2.98-2.90 (m, 1H), 2.02-1.90 (m, 1H), 1.83-1.74 (m, 1H), 1.64-1.53 (m, 2H), 1.50 (s, 9H).

後処理

  1. dissolutionuntil dissolved
  2. stirringstirred for 10 minutes
  3. stirringThe reaction was stirred for 30 minutes at 0° C
  4. temperatureto warm to ambient temperature
  5. stirringstirred overnight
  6. customThe reaction was quenched by addition of 1.5 M Na2SO3 (1 mL)
  7. stirringstirred for 15 minutes
  8. additionThe reaction mixture was diluted with Et2O
  9. customseparated
  10. washThe aqueous portion was washed (2×) with Et2O
  11. extractionThe aqueous portion was extracted (3×) with ethyl acetate
  12. washThe combined organic layers were washed with water (2×), saturated NaCl
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated in vacuo to a thick oil which

出典と根拠

ORDレコード
ord-1471244f7cba4b22b7d1006487a743aa
出典データセット
uspto-grants-2014_09
特許番号
US08841304B2

反応ノート

読み込み中…