Oxalyl chloride → 2'-Fluoro[1,1'-biphenyl]-4-carbonyl chloride

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Reaction Steps

Method B (e.g. methyl (2S,4EZ)-4-(methoxyimino)-1-[(2′-fluoro[1,1′-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxylate): To a solution of 2′-fluoro[1,1′-biphenyl]-4-carboxylic acid (69 mg, 0.32 mmol.) in 9 ml THF, were added oxalyl chloride (0.09 mL, 0.99 mmol) and DMF (three drops) under ice cooling. The mixture was stirred for 2 h at rt. The solvent was removed affording the corresponding acyl chloride, 2′-fluoro[1,1′biphenyl]-4-carbonyl chloride. The latter was now dissolved in THF (7 mL) and added slowly on a 0° C. solution containing the free NH-compound from the previous step, e.g. methyl (2S,4EZ)-4-(methoxyimino)-2-pyrrolidinecarboxylate (38 mg, 0.22 mmol), and triethylamine (2eq, 0.44 mmol, 0.06 ml) in THF/DCM 1:1 mixture (12 ml). The reaction mixture was stirred overnight at r.t. Pol-trisamine was added (69 mg, 3.45 mmol/g) in order to scavenge excess of acyl chloride. The mixture was shaken 5 h, filtered and the resulting solution was washed with NH4Cl 20%, brine, and dried over MgSO4. After filtration and evaporation of the solvents, the resulting dark oil (3.26 g) was purified by SPE (SAX sorbent) using neat DCM as eluent. The desired product, e.g. methyl (2S,4EZ)-4-(methoxyimino)-1-[(2′-fluoro[1,1′-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxylate was obtained as a mixture of two isomers as a white foam in 34% yield (97.3% purity by HPLC).

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