(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 1622213Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1622213
[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

Komponenten

5

Edukt 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

Produkt 1

HCID 534655661-(1,1-Dimethylethyl) 2-methyl (2S,4R)-4-(((4-bromo-1,3-dihydro-2H-isoindol-2-yl)carbonyl)oxy)-1,2-pyrrolidinedicarboxylateAusbeute 79,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-b639a1f1cafb4f62918b61d4b6583ca0
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08778877B2

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