1,1'-Carbonyldiimidazole → 1-t-Butyl 2-methyl (2S,4R)-4-{[(4-vinyl-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}pyrrolidine-1,2-dicarboxylate

HRID 1879250ノート

反応式

HRID 1879250 の反応式
[OH:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1.[C:18]([N:25]1[CH:29]=[CH:28]N=[CH:26]1)(N1C=CN=C1)=[O:19].[CH:30]([C:32]1C=[CH:39][CH:38]=[C:37]2[C:33]=1CNC2)=[CH2:31].S(=O)(=O)(O)[O-].[K+]>CN(C=O)C.O>[CH:38]([C:37]1[CH:33]=[CH:32][CH:30]=[C:31]2[C:28]=1[CH2:29][N:25]([C:18]([O:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1)=[O:19])[CH2:26]2)=[CH2:39]

参加物

7

反応物 4

HCID 682631,1'-CarbonyldiimidazoleHCID 516920Potassium bisulfateHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterHCID 534871884-Ethenyl-2,3-dihydro-1H-isoindole

生成物 1

HCID 453783721-t-Butyl 2-methyl (2S,4R)-4-{[(4-vinyl-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}pyrrolidine-1,2-dicarboxylate収率 81%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
60 °C

実験手順

A solution of 1-tert-butyl 2-methyl (2S,4R)-4-hydroxypyrrolidine-1,2-dicarboxylate (1.0 eq.) in DMF (0.5 M) under nitrogen was cooled to 0° C. Solid 1,1′-carbonyldiimidazole (1.0 eq.) was added to the reaction. The contents of the reaction flask were warmed to RT and after 2 h a solution of 4-vinylisoindoline (1.0 eq.) in DMF (4 M) was added. The reaction was heated in a 60° C. oil bath for 2 h then cooled and poured into water and 5% potassium bisulfate. The resulting mixture was extracted with EtOAc. Combined organics were washed with brine, dried with anhydrous sodium sulfate, filtered and evaporated. Flash column chromatography eluting with hexane/EtOAc 70/30 gave the title compound as a white foam (81%). LRMS (ESI) m/z 417 (M+H).

後処理

  1. additionwas added
  2. temperaturethen cooled
  3. extractionThe resulting mixture was extracted with EtOAc
  4. washCombined organics were washed with brine
  5. dry with materialdried with anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. washFlash column chromatography eluting with hexane/EtOAc 70/30

出典と根拠

ORDレコード
ord-00eb0678e2114a8298114d8ba159ba53
出典データセット
uspto-grants-2012_11
特許番号
US08314062B2

反応ノート

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