Water → 4-([3-(tert-butyldimethylsilanyloxy)phenyl]{3-[N-(3-fluorophenyl)-N-methylcarbamoyl]phenyl}-methylene)piperidine-1-carboxylic acid tert-butyl ester

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Reaction Steps

A mixture of 4-([3-(tert-butyldimethylsilanyloxy)phenyl]{3-[N-(3-fluorophenyl)-N-methyl-carbamoyl]phenyl}hydroxymethyl)piperidine-1-carboxylic acid tert-butyl ester (3.59 g) and p-toluenesulfonic acid monohydrate (3.5 g) in benzene (200 mL) was refluxed overnight in a round bottom flask equipped with Dean-Stark trap. The reaction solution was cooled to room temperature. Saturated Na2CO3 solution (50 mL) was added to the solution, followed by the addition of 100 mL of H2O. The resulting mixture was extracted by EtOAc (300 mL). It was observed that solids were floating between the two layers. Consequently, 75 ml of 0.5 M NaOH solution was added to the mixture. After being stirred for 30 minutes, the mixture became clear. The organic layer and water layer were separated. The water layer was extracted by EtOAc (100 mL×1). The combined organic layer was washed by water (75 mL×2) and brine (75 mL×1), dried by Na2SO4 and concentrated to give 4-([3-(tert-butyl-dimethylsilanyloxy)phenyl]{3-[N-(3-fluorophenyl)-N-methylcarbamoyl]phenyl}-methylene)piperidine-1-carboxylic acid tert-butyl ester (2.83 g; crude). TLC and 1H NMR of the crude product indicated a mixture of compounds, apparently including the desired dehydration product with the loss of N-Boc and/or O-TBDMS protecting groups. The crude product was carried to next step without purification.

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