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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).

1. extractionextracted with DCM
2. dry with materialThe combined organic phases were dried over magnesium sulfate
3. customSolvent removal
4. customafforded a crude product, which
5. customwas used without purification in the next step
6. dissolutionThe residue was dissolved in DCM at room temperature
7. temperatureto warm to room temperature
8. stirringUsually after 12 hours stirring at RT
9. washwashed with sodium carbonate solution (10%)
10. dry with materialdried over MgSO4
11. customevaporated in vacuo
12. customto give a crude product
13. washFlash chromatography on silica gel, eluting with 60% EtOAc in hexane