Reaktion #495790

Reaktionsgleichung

CDI

3-((4-chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-propionic acid

MgCl2

ethyl potassium malonate

→

5-((4-chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-3-oxo-pentanoic acid ethyl ester

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe reaction was stirred for 15 h at 20° C
2. 2
   EinengenThe crude was concentrated under reduced pressure
3. 3
   Sonstigethen partitioned between water and EtOAc
4. 4
   SonstigeThe layers were separated
5. 5
   Trocknenthe organic layer was dried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated under reduced pressure
8. 8
   SonstigeThe crude was purified by chromatography on silica gel (
9. 9
   Waschenelution with Hept/EtOAc/DCM/MeOH

Vorschrift

To a solution of CDI (4 eq) in THF was added 3-((4-chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-propionic acid, compound 65 (1 eq.), the mixture was stirred for 4 h at 20° C., then MgCl2 (4 eq.) and ethyl potassium malonate (5 eq.) were added. The reaction was stirred for 15 h at 20° C. The crude was concentrated under reduced pressure then partitioned between water and EtOAc. The layers were separated and the organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (elution with Hept/EtOAc/DCM/MeOH: 50/50/95/5 then 50/50/90/10) to afford 5-((4-chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-3-oxo-pentanoic acid ethyl ester.

Quelle