Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][CH3:19])=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([CH:14]=O)=[CH:10][C:9]=2[O:16][CH3:17])[CH:7]=1.Cl.[O:21]([NH2:23])[CH3:22]>N1C=CC=CC=1>[CH3:22][O:21][N:23]=[CH:14][C:11]1[CH:12]=[CH:13][C:8]([C:6]2[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[O:18][CH3:19])=[C:9]([O:16][CH3:17])[CH:10]=1
Reactant: COc1cc(C=O)ccc1-c1cc(F)ccc1OC
Reactant: CON
Agent: Cl
Solvent: c1ccncc1
Product: CON=Cc1ccc(-c2cc(F)ccc2OC)c(OC)c1
Reaction time: 16 h
Yield: 39.6 %

Procedure:
To a stirred solution of 4-hydroxy-3-methoxybenzaldehyde (2 g, 14.7 mmol) in dichloromethane (20 ml) was slowly added trifluoromethanesulfonic anhydride (4.5 g, 17.64 mmol) and pyridine (1.5 ml, 14.7 mmol) at 0° C. under nitrogen atmosphere. The solution was stirred for 16 h at ambient temperature, ice-water slurry added and then extracted with dichloromethane. The combined extracts were dried over anhydrous sodium sulfate and the solvent evaporated. The residue was flash chromatographed over silica gel eluting with 4:1 heptane/ethyl acetate and the solvent evaporated to give trifluoromethanesulfonic acid-4-formyl-2-methoxy-phenyl ester (3.5 g) as colourless oil. To a stirred solution of trifluoromethanesulfonic acid-4-formyl-2-methoxy-phenyl ester (3.5 g, 12.3 mmol) in tetrahydrofuran (50 ml) was added 5-fluoro-2-methoxyphenyl boronic acid, lithium chloride (0.05 g, 1.18 mmol), 2M sodium carbonate (14 ml) and tetrakis(triphenylphosphine)palladium (0) (0.22 g, 0.18 mmol). The reaction mixture was refluxed for 5 days then concentrated under reduced pressure. The concentrate was dissolved in ethyl acetate, washed with water, dried over sodium sulfate and the solvent evaporated. The residue was flash chromatographed over silica gel eluting with 5:1 heptane/ethyl acetate and the solvent evaporated to give 5′-fluoro-2,2′-dimethoxy-biphenyl-4-carbaldehyde (2.65 g) as a yellow oil. To a stirred solution of 5′-fluoro-2,2′-dimethoxy-biphenyl-4-carbaldehyde (2.65 g, 9.16 mmol) in pyridine (50 ml) was added methoxylamine hydrochloride (0.474 g, 10.1 mmol) at ambient temperature under nitrogen atmosphere. The reaction mixture was stirred for 16 h. Following evaporation of pyridine under reduced pressure, the residue was dissolved in dichloromethane, washed with water and dried over anhydrous sodium sulfate. Evaporation of solvent followed by purification on a SCX column eluting with methanol gave 5′-fluoro-2,2′-dimethoxy-biphenyl-4-carbaldehyde-O-methyl-oxime (1.05 g) as an oil. A stirred solution of 5′-fluoro-2,2′-dimethoxy-biphenyl-4-carbaldehyde-O-methyl-oxime (0.182 g, 0.63 mmol) and 10% palladium on activated carbon in ethanol (10 ml) and 2M hydrogen chloride (5 drops) was degassed at ambient temperature then purged with hydrogen at atmospheric pressure for 16 h in a sealed vessel. The reaction mixture was then filtered through dicalite and evaporated. The residue was basified to pH 11 with aqueous sodium carbonate, extracted with dichloromethane and dried over anhydrous sodium sulfate. Evaporation of solvent gave C-(5′-fluoro-2,2′-dimethoxy-biphenyl-4-yl)-methylamine (0.27 g) as a gum. To a stirred solution of C-(5′-fluoro-2,2′-dimethoxy-biphenyl-4-yl)-methylamine in dichloromethane (5 ml) was added 4-methoxybenzene sulfonyl chloride (0.03 g, 0.12 mmol) and triethylamine (0.034 ml, 0.24 mmol). The reaction mixture was stirred for 16 h. Water was added and the mixture was filtered through a hydrophobic filter, then flash chromatographed over a SCX column eluting with methanol. Purification by preparatory LCMS and removal of solvent under reduced pressure gave the title compound (0.01 g) as gum: MS (ESI) m/z: 432.3 [M+H]+.