1,1'-Carbonyldiimidazole → (2RS)-2-(2,4-difluorophenyl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-ethanoic acid

HRID 383969

Reaktionsgleichung

Reaktionsgleichung von HRID 383969
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]([N:20]1[C@H:25]([CH2:26][CH:27]([CH3:29])[CH3:28])[C:24](=[O:30])[NH:23][C@H:22]([CH:31]2[CH2:39][C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH2:32]2)[C:21]1=[O:40])[C:10](NC1C=CC=CC=1O)=[O:11].C(N1C=CN=C1)(N1C=CN=C1)=[O:42]>ClCCl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]([N:20]1[C@H:25]([CH2:26][CH:27]([CH3:28])[CH3:29])[C:24](=[O:30])[NH:23][C@H:22]([CH:31]2[CH2:32][C:33]3[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:39]2)[C:21]1=[O:40])[C:10]([OH:42])=[O:11]

Komponenten

4

Edukt 2

HCID 682631,1'-CarbonyldiimidazoleHCID 11649656(2RS)-2-(2,4-difluorophenyl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-N-(2-hydroxyphenyl)ethanamide

Produkt 1

HCID 68844874(2RS)-2-(2,4-difluorophenyl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-ethanoic acidAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

(2RS)-2-(2,4-difluorophenyl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-N-(2-hydroxyphenyl)ethanamide (2.650 g) was stirred in dichloromethane (20 ml) and carbonyldiimidazole (1.178 g) was added. the mixture was left at room temperature for 16 hours then the solvent was removed under reduced pressure. The residue was then taken up in 1:1 acetone:water (v/v) (80 ml) and left at room temperature for 30 minutes. The bulk of the acetone was then removed under reduced pressure and the residue was partitioned between dichloromethane and 0.5M hydrochloric acid. The organic phase was separated (hydrophobic frit) and evaporated under reduced pressure. The crude product was purified (Biotage™ flash chromatography column, 90 g silica cartridge eluted with (i) 1:1 ethyl acetate:cyclohexane (ii) ethyl acetate (iii) ethyl acetate:methanol 9:1) to afford (2RS)-2-(2,4-difluorophenyl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-ethanoic acid as a colourless solid 1.524 g as a mixture of epimers.

Aufarbeitung

  1. customthe solvent was removed under reduced pressure
  2. waitwater (v/v) (80 ml) and left at room temperature for 30 minutes
  3. customThe bulk of the acetone was then removed under reduced pressure
  4. customthe residue was partitioned between dichloromethane and 0.5M hydrochloric acid
  5. customThe organic phase was separated (hydrophobic frit)
  6. customevaporated under reduced pressure
  7. customThe crude product was purified
  8. wash(Biotage™ flash chromatography column, 90 g silica cartridge eluted with (i) 1:1 ethyl acetate:cyclohexane (ii) ethyl acetate (iii) ethyl acetate:methanol 9:1)

Quellen und Nachweise

ORD-Eintrag
ord-14ef7acde02f440d9ef8ebcb9e04bbfe
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08367673B2

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