Potassium Carbonate → Methyl 1-{[(4'-chloro-3'-fluoro-4-methylbiphenyl-3-yl)acetyl]amino}-4,4-difluorocyclohexanecarboxylate

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Reaction Conditions

Reaction Steps

6.06 g (21.7 mmol) of the compound from Example 1A were dissolved in 7.5 ml (103 mmol) of thionyl chloride. The reaction mixture was stirred at 80° C. for 1 h and then concentrated. The residue was dissolved in 30 ml of acetonitrile. Ethyl acetate and saturated aqueous sodium bicarbonate solution were added to 5.00 g (21.8 mmol) of the compound from Example 4A. The phases were separated, the aqueous phase was extracted repeatedly with ethyl acetate and the combined organic phases were dried over sodium sulfate, filtered and concentrated. 140 ml of acetonitrile and 8.76 g (63.4 mmol) of potassium carbonate were added to the residue. With ice-cooling, the solution of the acid chloride was added dropwise, and the mixture was stirred at room temperature overnight. The mixture was then added to ice-water and extracted repeatedly with dichloromethane, and the combined organic phases were washed repeatedly with 1N aqueous hydrogen chloride solution and saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated. This gave 8.22 g (83% of theory) of the title compound, which were converted without further purification.

Provenance & Evidence