(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester → 1-(1,1-Dimethylethyl) 2-methyl (2S,4R)-4-(((4-bromo-1,3-dihydro-2H-isoindol-2-yl)carbonyl)oxy)-1,2-pyrrolidinedicarboxylate

HRID 1622213ノート

反応式

HRID 1622213 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](C1NC=CN=1)(C1NC=CN=1)=[O:19].[Br:30][C:31]1[C:32]2[C:36]([CH:37]=[CH:38][CH:39]=1)=[CH:35][NH:34][CH:33]=2>CN(C)C(=O)C>[Br:30][C:31]1[CH:39]=[CH:38][CH:37]=[C:36]2[C:32]=1[CH2:33][N:34]([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])[CH2:35]2

参加物

5

反応物 3

HCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 540199984-Bromoisoindole

生成物 1

HCID 534655661-(1,1-Dimethylethyl) 2-methyl (2S,4R)-4-(((4-bromo-1,3-dihydro-2H-isoindol-2-yl)carbonyl)oxy)-1,2-pyrrolidinedicarboxylate収率 79.4%

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
60 °C

実験手順

To a solution containing 0.5 g of (2S,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (2 mmol) in 5 mL of N,N-dimethylacetamide, was added 370 mg of carbonyl diimidazole (1.1 equiv.). The reaction was heated at 60° C. for 1 hr, then 400 mg of 4-bromoisoindole (2 mmol) was added. The reaction was continued at 60° C. overnight. After cooling down, the reaction mixture was extracted with 50 mL of EtOAc, and washed with water, brine, and dried over Na2SO4. After filtration and concentration, the residue was purified by flash column chromatography on silica gel using heptanes/EtOAc (v/v 5/2), giving white solid 745 mg (79%). LC-MS: m/z=369.2 (ES+, M+1-Boc).

後処理

  1. temperatureAfter cooling down
  2. extractionthe reaction mixture was extracted with 50 mL of EtOAc
  3. washwashed with water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationAfter filtration and concentration
  6. customthe residue was purified by flash column chromatography on silica gel

出典と根拠

ORDレコード
ord-b639a1f1cafb4f62918b61d4b6583ca0
出典データセット
uspto-grants-2014_07
特許番号
US08778877B2

反応ノート

読み込み中…