1,2-Dichloroethane → N-({3-[(2S,4EZ)-1-([1,1'-biphenyl]-4-ylcarbonyl)-4-(methoxyimino)-pyrrolidinyl]-1,2,4-oxadiazol-5-yl}methyl)-2-(dimethylamino)acetamide

Participants

Reaction Conditions

Reaction Steps

4-{[(2S,4EZ)-2-(5-{[(tert-butoxycarbonyl)amino]methyl}-1,2,4-oxadiazol-3-yl)-4-(methoxyimino)pyrrolidinyl]carbonyl}-1,1′-biphenyl (Example 50) was treated with a 25% TFA/DCM solution at 0° C. The reaction was monitored by LC/MS and stopped after completion. The reaction was then made basic with sodium carbonate solution (10%) and extracted with DCM. The combined organic phases were dried over magnesium sulfate. Solvent removal afforded a crude product, which was used without purification in the next step. The residue was dissolved in DCM at room temperature, DMAP (1.1 equivalent) and (dimethylamino)acetic acid (1 equivalent) were added. The reaction mixture was then cooled down to 0° C. and EDC (1.1 equivalent) was added portion-wise. After stirring for 1 hour at 0° C., the reaction mixture was allowed to warm to room temperature. The reaction was monitored by TLC and LC/MS. Usually after 12 hours stirring at RT, the reaction mixture was hydrolyzed, washed with sodium carbonate solution (10%), dried over MgSO4, and evaporated in vacuo to give a crude product. Flash chromatography on silica gel, eluting with 60% EtOAc in hexane, gave the title compound as a mixture of E- and Z-isomers in 45% yield (88.1% purity by HPLC).

Provenance & Evidence