Potassium Carbonate → Methyl 1-{[(4'-chloro-4-methylbiphenyl-3-yl)acetyl]amino}-4-methoxy-4-(methoxymethyl)cyclohexanecarboxylate

Participants

Reaction Conditions

Reaction Steps

574 mg (2.20 mmol) of (4′-chloro-4-methylbiphenyl-3-yl)acetic acid (EP 2029531 A1 and US 2009/298828 A1) were dissolved in 0.9 g (12.5 mmol) of thionyl chloride. The reaction mixture was stirred at 80° C. for 1 h and then concentrated. The residue was dissolved in 5 ml of acetonitrile. 816 mg (5.90 mmol) of potassium carbonate were added to 390 mg (1.69 mmol) of the compound from Example 24A in 10 ml of acetonitrile. 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 concentrated, the residue was taken up in 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 sulphate, filtered and concentrated. This gave 570 mg of the title compound as a diastereomer mixture which were reacted without further purification.

Provenance & Evidence